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Raffa S, Lanfranchi F, Satragno C, Giannelli F, Marcenaro M, Coco A, Cena SE, Sofia L, Marini C, Mammoliti S, Levaggi A, Tagliafico AS, Sambuceti G, Barra S, Morbelli S, Belgioia L, Bauckneht M. The prognostic value of FIGO staging defined by combining MRI and [ 18F]FDG PET/CT in patients with locally advanced cervical cancer. Curr Probl Cancer 2023; 47:101007. [PMID: 37684197 DOI: 10.1016/j.currproblcancer.2023.101007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 08/08/2023] [Accepted: 08/16/2023] [Indexed: 09/10/2023] [Imported: 09/28/2023]
Abstract
The last version of the FIGO classification recommended imaging tools to complete the clinical assessment of patients with cervical cancer. However, the preferable imaging approach is still unclear. We aimed to explore the prognostic power of Magnetic Resonance Imaging (MRI), contrast-enhanced Computed Tomography (ceCT), and [18F]-Fluorodeoxyglucose Positron Emission Tomography ([18F]FDG-PET)/CT in patients staged for locally advanced cervical cancer (LACC, FIGO stages IB3-IVA). Thirty-six LACC patients (mean age 55.47 ± 14.01, range 31-82) were retrospectively enrolled. All of them underwent MRI, ceCT and [18F]FDG-PET/CT before receiving concurrent chemoradiotherapy. A median dose of 45 Gy (range 42-50.4; 25-28 fractions, 5 fractions per week, 1 per day) was delivered through the external-beam radiation therapy (EBRT) on the pelvic area, while a median dose of 57.5 Gy (range 16-61.1; 25-28 fractions, 5 fractions per week, 1 per day) was administered on metastatic nodes. The median doses for brachytherapy treatment were 28 Gy (range 28-30; 4-5 fractions, 1 every other day). Six cycles of cisplatin or carboplatin were administered weekly. The study endpoints were recurrence-free survival (RFS) and overall survival (OS). Metastatic pelvic lymph nodes at MRI independently predicted RFS (HR 13.271, 95% CI 1.730-101.805; P = 0.027), while metastatic paraaortic lymph nodes at [18F]FDG-PET/CT independently predicted both RFS (HR 11.734, 95% CI 3.200-43.026; P = .005) and OS (HR 13.799, 95% CI 3.378-56.361; P < 0.001). MRI and [18F]FDG-PET/CT findings were incorporated with clinical evidences into the FIGO classification. With respect to the combination of clinical, MRI and ceCT data, the use of next-generation imaging (NGI) determined a stage migration in 10/36 (27.7%) of patients. Different NGI-based FIGO classes showed remarkably different median RFS (stage IIB: not reached; stage IIIC1: 44 months; stage IIIC2: 3 months; P < 0.001) and OS (stage IIB: not reached; stage IIIC1: not reached; stage IIIC2: 14 months; P < 0.001). A FIGO classification based on the combination of MRI and [18F]FDG-PET/CT might predict RFS and OS of LACC patients treated with concurrent chemoradiotherapy.
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Cuccia F, Pastorello E, Franzese C, Belgioia L, Bignardi M, Federico M, Figlia V, Giaj Levra N, Badellino S, Borghetti P, Marvaso G, Montesi G, Pontoriero A, Fazio I, Ferrera G, Alongi F, Scorsetti M. Stereotactic Body Radiotherapy for Spine Oligometastases: A Multicentre Retrospective Study From the Italian Association of Radiotherapy and Clinical Oncology (AIRO). Clin Oncol (R Coll Radiol) 2023; 35:794-800. [PMID: 37714793 DOI: 10.1016/j.clon.2023.09.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 07/26/2023] [Accepted: 09/04/2023] [Indexed: 09/17/2023] [Imported: 09/28/2023]
Abstract
AIM To evaluate the efficacy of stereotactic body radiotherapy (SBRT) for spine oligometastases. MATERIALS AND METHODS This was a multicentre retrospective study of a series of patients who received SBRT for spine oligometastases. The efficacy of SBRT was evaluated in terms of local control as the primary endpoint. Survival outcomes were also analysed to identify predictive factors for clinical outcomes. Toxicity was assessed according to CTCAE v4.0. RESULTS Between March 2018 and July 2022, 183 lesions in 177 patients were analysed. In most patients, SBRT was delivered to a single spine metastasis (82%) for a median total dose of 21 Gy (14-35 Gy) in three fractions (one to five fractions) and a median BED10 = 119 Gy (57.7-152 Gy). Local control rates were 90.3% at 1 year, 84.3% at 2 years and 84.3% at 3 years. Distant progression-free survival rates were 33.1%, 18.5% and 12.4% at 1, 2 and 3 years, with prostate histology (P = 0.023), oligorecurrent disease (P = 0.04) and BED10 > 100 Gy (P = 0.04) found to be predictive on univariate analysis. A further oligometastatic progression was observed in 33 patients (18.6%) treated with a second course of SBRT, reporting at univariate analysis improved overall survival rates (P = 0.01). Polymetastases-free survival rates were 57.8%, 43.4% and 32.4%; concurrent therapy was related to improved outcomes at multivariate analysis (P = 0.009). Overall survival rates were 91.8%, 79.6% and 65.9%, with prostate histology and non-cervical metastases related to better overall survival at multivariate analysis. Pain-flare after SBRT was recorded in 3.3%; five patients underwent surgical decompression after SBRT; there were no grade ≥3 adverse events. CONCLUSIONS In our experience of only oligometastatic patients, spine SBRT gave excellent results in terms of safety and efficacy. Prostate histology and oligorecurrent disease were predictive factors for improved clinical outcomes; also, patients who experienced a further oligoprogression after SBRT maintained a survival advantage compared with polymetastatic progression. No severe adverse events were reported.
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Arcelli A, Tarantino G, Cellini F, Buwenge M, Macchia G, Bertini F, Guido A, Deodato F, Cilla S, Scotti V, Rosetto ME, Djan I, Parisi S, Mattiucci GC, Fiore M, Bonomo P, Belgioia L, Niespolo RM, Gabriele P, Di Marco M, Simoni N, Ma J, Strigari L, Mazzarotto R, Morganti AG. Comparative Effectiveness of Chemotherapy Alone Versus Radiotherapy-Based Regimens in Locally Advanced Pancreatic Cancer: A Real-World Multicenter Analysis (PAULA-1). Curr Oncol 2023; 30:5690-5703. [PMID: 37366910 DOI: 10.3390/curroncol30060427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/30/2023] [Accepted: 06/04/2023] [Indexed: 06/28/2023] [Imported: 09/01/2023] Open
Abstract
Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a real-world setting in terms of overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). LAPC patients from a multicentric retrospective database were included (2005-2018). Survival curves were calculated using the Kaplan-Meier method. Multivariable Cox analysis was performed to identify predictors of LC, OS, and DMFS. Of the 419 patients included, 71.1% were treated with CRT, 15.5% with CHT, and 13.4% with SBRT. Multivariable analysis showed higher LC rates for CRT (HR: 0.56, 95%CI 0.34-0.92, p = 0.022) or SBRT (HR: 0.27, 95%CI 0.13-0.54, p < 0.001), compared to CHT. CRT (HR: 0.44, 95%CI 0.28-0.70, p < 0.001) and SBRT (HR: 0.40, 95%CI 0.22-0.74, p = 0.003) were predictors of prolonged OS with respect to CHT. No significant differences were recorded in terms of DMFS. In selected patients, the addition of radiotherapy to CHT is still an option to be considered. In patients referred for radiotherapy, CRT can be replaced by SBRT considering its duration, higher LC rate, and OS rate, which are at least comparable to that of CRT.
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Fozza A, De Rose F, De Santis MC, Meattini I, Meduri B, D'Angelo E, Dei D, Figlia V, La Rocca E, Fregatti P, Satragno C, Belgioia L, Giaj-Levra N. Technological advancements and future perspectives in breast cancer radiation therapy. Expert Rev Anticancer Ther 2023; 23:407-419. [PMID: 36960754 DOI: 10.1080/14737140.2023.2195167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2023] [Imported: 09/01/2023]
Abstract
INTRODUCTION Breast cancer is still one of the most common tumors worldwide and radiation therapy has a central role in the oncological pathway. Several technological options are now available with the aim to improve therapeutic index, target definition, and patient selection. AREAS COVERED In this review, we summarize current available technologies in the management of breast cancer. These advances can support the prescription of postoperative partial breast cancer treatment and preoperative stereotactic partial breast irradiation. Moreover, image-guided radiotherapy is crucial for high quality radiation treatments. Additionally, the recent development of hybrid magnetic resonance linear accelerator can impact in target volume outline procedure, adaptive planning and radiomics. Finally, artificial intelligence represents the new frontier in medicine, supporting clinicians in target definition, patient selection, and treatment planning. EXPERT OPINION In patients with breast cancer the overall level of evidence about new technologies is still low even if some advances are potentially very interesting to further development.
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Dionisi F, Di Rito A, Errico A, Iaccarino G, Farneti A, D'Urso P, Nardangeli A, Bambace S, D'Onofrio I, D'Angelo E, De Felice F, Fanetti G, Belgioia L, Alterio D, Orlandi E, Merlotti A, Musio D, Sanguineti G. Nasopharyngeal cancer: the impact of guidelines and teaching on radiation target volume delineation. LA RADIOLOGIA MEDICA 2023; 128:362-371. [PMID: 36877421 DOI: 10.1007/s11547-023-01612-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 02/16/2023] [Indexed: 03/07/2023] [Imported: 09/01/2023]
Abstract
Target volume delineation in the radiation treatment of nasopharyngeal cancer is challenging due to several reasons such as the complex anatomy of the site, the need for the elective coverage of definite anatomical regions, the curative intent of treatment and the rarity of the disease, especially in non-endemic areas. We aimed to analyze the impact of educational interactive teaching courses on target volume delineation accuracy between Italian radiation oncology centers. Only one contour dataset per center was admitted. The educational course consisted in three parts: (1) The completely anonymized image dataset of a T4N1 nasopharyngeal cancer patient was shared between centers before the course with the request of target volume and organs at risk delineation; (2) the course was held online with dedicated multidisciplinary sessions on nasopharyngeal anatomy, nasopharyngeal cancer pattern of diffusion and on the description and explanation of international contouring guidelines. At the end of the course, the participating centers were asked to resubmit the contours with appropriate corrections; (3) the pre- and post-course contours were analyzed and quantitatively and qualitatively compared with the benchmark contours delineated by the panel of experts. The analysis of the 19 pre- and post-contours submitted by the participating centers revealed a significant improvement in the Dice similarity index in all the clinical target volumes (CTV1, CTV2 and CTV3) passing from 0.67, 0.51 and 0.48 to 0.69, 0.65 and 0.52, respectively. The organs at risk delineation was also improved. The qualitative analysis consisted in the evaluation of the inclusion of the proper anatomical regions in the target volumes; it was conducted following internationally validated guidelines of contouring for nasopharyngeal radiation treatment. All the sites were properly included in target volume delineation by >50% of the centers after correction. A significant improvement was registered for the skull base, the sphenoid sinus and the nodal levels. These results demonstrated the important role that educational courses with interactive sessions could have in such a challenging task as target volume delineation in modern radiation oncology.
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Chiloiro G, Romano A, Mariani S, Macchia G, Giannarelli D, Caravatta L, Franco P, Boldrini L, Arcelli A, Bacigalupo A, Belgioia L, Fontana A, Meldolesi E, Montesi G, Niespolo RM, Palazzari E, Piva C, Valentini V, Gambacorta MA. Predictive and prognostic value of inflammatory markers in locally advanced rectal cancer (PILLAR) - A multicentric analysis by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Gastrointestinal Study Group. Clin Transl Radiat Oncol 2023; 39:100579. [PMID: 36935859 PMCID: PMC10014327 DOI: 10.1016/j.ctro.2023.100579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/08/2023] [Accepted: 01/09/2023] [Indexed: 01/13/2023] [Imported: 09/01/2023] Open
Abstract
Background Patients (pts) affected with locally advanced rectal cancer (LARC) may respond differently to neoadjuvant chemoradiotherapy (nCRT). The identification of reliable biomarkers able to predict oncological outcomes could help in the development of risk-adapted treatment strategies. It has been suggested that inflammation parameters may have a role in predicting tumor response to nCRT and survival outcomes and in rectal cancer, but no definitive conclusion can be drawn at present. The aim of the current study is to evaluate the role of baseline inflammatory markers as prognostic and predictive factors in a large multicentric Italian cohort of LARC pts. Methods Patients diagnosed with LARC from January 2002 to December 2019 in 9 Italian centers were retrospectively collected. Patients underwent long-course RT with chemotherapy based on fluoropyrimidine ± oxaliplatin followed by surgery. Inflammatory markers were retrieved based on a pre-treatment blood sample including HEI (hemo-eosinophils inflammation index), SII (systemic index of inflammation), NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) and MLR (monocyte-to-lymphocyte ratio). Outcomes of interest were pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). Results 808 pts were analyzed. pCR rate was 22 %, 5yOS and 5yDFS were 84.0% and 63.1% respectively. Multivariate analysis identified that a NLR cut-off value >1.2 and SII cut-off value >500 could predict pCR (p = 0.05 and 0.009 respectively). In addition to age, extramesorectal nodes and RT dose, MLR >0.18 (p = 0.03) and HEI = 3 (p = 0.05) were independent prognostic factors for DFS. Finally, age, RT dose, MLR with a cut-off >0.35 (p = 0.028) and HEI = 3 (p = 0.045) were independent predictors of OS. Conclusions Higher values of baseline composite inflammatory markers can serve as predictors of lower pCR rates and worse survival outcomes in LARC patients undergoing nCRT. More reliable data from prospective studies could lead to the integration of these inexpensive and easy-to-derive tools into clinical practice.
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Di Franco R, Pezzulla D, Arcidiacono F, Pontoriero A, Cellini F, Belgioia L, Borzillo V, Lillo S, Pastore F, Dominici L, Longo S, Cacciola A, Ciabattoni A, Zamagni A, Francolini G, Fontana A, Scipilliti E, Mazzola R, D'Angelo E, Ingargiola R, Muto P, Maranzano E. Reirradiation on spine metastases: an Italian survey on behalf of palliative care and reirradiation study groups of Italian association of radiotherapy and clinical oncology (AIRO). CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2023; 25:408-416. [PMID: 36163444 DOI: 10.1007/s12094-022-02951-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 09/07/2022] [Indexed: 01/27/2023] [Imported: 09/01/2023]
Abstract
AIM This survey derived from the collaboration between the Palliative Care and Reirradiation Study Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO). Its aim was to obtain a real "snapshot" on the treatments of spinal metastases, focusing on reirradiation, among radiation oncologists in Italy. METHODS The survey was elaborated on SurveyMonkey's online interface and was sent via e-mail to all Radiation Oncologists of AIRO that were invited to anonymously fill in the electronic form within 60 days. The questionnaire was prepared by the AIRO "Palliative care" and "Reirradiation" Study Groups and it consisted of 36 questions, 19 single-choice questions, 10 multiple-choice questions and 6 open questions. The data were analyzed and represented with tables and graphs. RESULTS The survey shows that palliative radiotherapy remains a field of interest for most ROs in the Italian centers. 3D Conventional Radiation Therapy (3DCRT) alone or in combination with other techniques is the primary choice for patients with a life expectancy of less than 6 months. For patients with a life expectancy of more than six months, there is an increased use of new technologies, such as Volumetric Modulated Arc Therapy (VMAT). Factors considered for retreatment are time between first and second treatment, dose delivered to spine metastasis and spinal cord in the first treatment, vertebral stability, symptoms, and/or performance status. The most feared complication are myelopathy followed by vertebral fracture and local recurrence. This explain an increasing focus on patient selection and the use of high technology in the treatment of metastatic patients. CONCLUSION Stereotactic body radiotherapy (SBRT) and image-guided radiotherapy allow the administration of ablative RT doses while sparing the constraints of healthy tissue in spinal metastases. However, there is still an unclear and heterogeneous reality in the reirradiation of spinal metastases. A national registry with the aim of clarifying the most controversial aspects of vertebral metastasis retreatments will enable better management of these patients and design more targeted study designs.
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Oligometastatic Prostate Cancer Treated with Metastasis-Directed Therapy Guided by Positron Emission Tomography: Does the Tracer Matter? Cancers (Basel) 2023; 15:cancers15010323. [PMID: 36612319 PMCID: PMC9818332 DOI: 10.3390/cancers15010323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/23/2022] [Accepted: 12/30/2022] [Indexed: 01/06/2023] [Imported: 09/01/2023] Open
Abstract
The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT. Thirty-seven oligometastatic PCa patients treated with PET-guided MDT were retrospectively enrolled. MDT was guided by [18F]F-Fluorocholine PET/CT in eleven patients and by [68Ga]Ga-PSMA-11 PET/CT in twenty-six. Progression was defined as biochemical recurrence (BR), radiological progression at subsequent PET/CT imaging, clinical progression, androgen deprivation therapy initiation, or death. Clinical and imaging parameters were assessed as predictors of PFS. [18F]F-Fluorocholine PET-guided MDT was associated with significantly lower PFS compared to the [68Ga]Ga-PSMA-11 group (median PFS, mPFS 15.47 months, 95% CI: 4.13−38.00 vs. 40.93 months, 95% CI: 40.93−40.93, respectively; p < 0.05). Coherently, the radiotracer used for PET-guided MDT resulted in predictive PFS at the univariate analysis, as well as the castration-resistant status at the time of MDT and the PSA nadir after MDT. However, in the multivariate analysis, castration resistance and PSA nadir after MDT remained the sole independent predictors of PFS. In conclusion, in the present proof-of-concept study, [68Ga]Ga-PSMA-11 provided higher PFS rates than [18F]F-Fluorocholine imaging in oligometastatic PCa patients receiving PET-guided MDT. Although preliminary, this finding suggests that enlarging the “tip of the iceberg”, by detecting a major proportion of the submerged disease thanks to next-generation imaging may favourably impact the oncological outcome of oligometastatic PCa treated with MDT.
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Merlotti A, Alterio D, Orlandi E, Racadot S, Bonomo P, Franco P, D'Angelo E, Ursino S, Pointreau Y, Lapeyre M, Graff P, Di Rito A, Argenone A, Musio D, De Felice F, Dionisi F, Fanetti G, D'Onofrio I, Belgioia L, Maddalo M, Scricciolo M, Bourhis J, Russi E, Thariat J. AIRO GORTEC consensus on postoperative radiotherapy (PORT) in low-intermediate risk early stages oral squamous cell cancers (OSCC). Radiother Oncol 2022; 177:95-104. [PMID: 36336113 DOI: 10.1016/j.radonc.2022.10.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 10/19/2022] [Accepted: 10/30/2022] [Indexed: 11/06/2022] [Imported: 09/01/2023]
Abstract
Evidence on the efficacy of postoperative radiotherapy (PORT) in low-intermediate risk squamous cell carcinoma of the oral cavity (OSCC) remains inconclusive. Members of a task force from two national radio-oncology Associations (AIRO and GORTEC) defined 14 clinically relevant questions to identify "gray areas" pertinent to the indication for PORT in this clinical setting. Consequently, a literature review was performed on the topic. The resulting statements were then rated by an Expert Panel (EP) using a modified Delphi method. Only radiation oncologists were part of the discussion and voting on the scenarios. There was agreement on the 14 statements at the first round of voting. The task force then decided to propose clinical cases for the two more controversial statements that had received a lower agreement to better capture the Experts' attitudes. The clinical cases highlighted a more significant decisional heterogeneity. However, the good level of consensus reached among the two Associations gives relevant support in informing clinical choices while acknowledging general indications cannot fit all clinical situations and do not replace multidisciplinary discussion.
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Satragno C, Verrico A, Giannelli F, Ferrero A, Campora S, Turazzi M, Cavagnetto F, Schiavetti I, Garrè ML, Garibotto F, Milanaccio C, Piccolo G, Crocco M, Ramaglia A, Di Profio S, Barra S, Belgioia L. High dose craniospinal irradiation as independent risk factor of permanent alopecia in childhood medulloblastoma survivors: cohort study and literature review. J Neurooncol 2022; 160:659-668. [PMID: 36369416 PMCID: PMC9758075 DOI: 10.1007/s11060-022-04186-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 10/28/2022] [Indexed: 11/13/2022] [Imported: 09/01/2023]
Abstract
PURPOSE Our aim was to determine the main risk factors related to the occurrence of permanent alopecia in childhood medulloblastoma (MB) survivors. METHODS We retrospectively analyzed the clinical features of all consecutive MB survivors treated at our institute. We divided the patients into 3 groups depending on the craniospinal irradiation (CSI) dose received and defined permanent alopecia first in terms of the skin region affected (whole scalp and nape region), then on the basis of the toxicity degree (G). Any relationship between permanent alopecia and other characteristics was investigated by a univariate and multivariate analysis and Odds ratio (OR) with confidence interval (CI) was reported. RESULTS We included 41 patients with a mean10-year follow-up. High dose CSI resulted as an independent factor leading to permanent hair loss in both groups: alopecia of the whole scalp (G1 p-value 0.030, G2 p-value 0.003) and of the nape region (G1 p-value 0.038, G2 p-value 0.006). The posterior cranial fossa (PCF) boost volume and dose were not significant factors at multivariate analysis neither in permanent hair loss of the whole scalp nor only in the nuchal region. CONCLUSION In pediatric patients with MB, the development of permanent alopecia seems to depend only on the CSI dose ≥ 36 Gy. Acute damage to the hair follicle is dose dependent, but in terms of late side effects, constant and homogeneous daily irradiation of a large volume may have a stronger effect than a higher but focal dose of radiotherapy.
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Myeloma Spine and Bone Damage Score (MSBDS) on Whole-Body Computed Tomography (WBCT): Multiple Reader Agreement in a Multicenter Reliability Study. Diagnostics (Basel) 2022; 12:diagnostics12081894. [PMID: 36010244 PMCID: PMC9407006 DOI: 10.3390/diagnostics12081894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/19/2022] [Accepted: 08/02/2022] [Indexed: 11/24/2022] [Imported: 09/01/2023] Open
Abstract
Objective: To assess the reliability of the myeloma spine and bone damage score (MSBDS) across multiple readers with different levels of expertise and from different institutions. Methods: A reliability exercise, including 104 data sets of static images and complete CT examinations of patients affected by multiple myeloma (MM), was performed. A complementary imaging atlas provided detailed examples of the MSBDS scores, including low-risk and high-risk lesions. A total of 15 readers testing the MSBDS were evaluated. ICC estimates and their 95% confidence intervals were calculated based on mean rating (k = 15), absolute agreement, a two-way random-effects model and Cronbach’s alpha. Results: Overall, the ICC correlation coefficient was 0.87 (95% confidence interval: 0.79–0.92), and the Cronbach’s alpha was 0.93 (95% confidence interval: 0.94–0.97). Global inter- and intra-observer agreement among the 15 readers with scores below or equal to 6 points and scores above 6 points were 0.81 (95% C.I.: 0.72–0.86) and 0.94 (95% C.I.:0.91–0.98), respectively. Conclusion: We present a consensus-based semiquantitative scoring systems for CT in MM with a complementary CT imaging atlas including detailed examples of relevant scoring techniques. We found substantial agreement among readers with different levels of experience, thereby supporting the role of the MSBDS for possible large-scale applications. Significance and Innovations • Based on previous work and definitions of the MSBDS, we present real-life reliability data for quantitative bone damage assessment in multiple myeloma (MM) patients on CT. • In this study, reliability for the MSBDS, which was tested on 15 readers with different levels of expertise and from different institutions, was shown to be moderate to excellent. • The complementary CT imaging atlas is expected to enhance unified interpretations of the MSBDS between different professionals dealing with MM patients in their routine clinical practice.
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Miccichè F, Chiloiro G, Longo S, Autorino R, Massaccesi M, Lenkowicz J, Bonomo P, Desideri I, Belgioia L, Bacigalupo A, D’Angelo E, Bertolini F, Merlotti A, Denaro N, Franco P, Bussu F, Paludetti G, Ricardi U, Valentini V. Development of a prognostic model of overall survival in oropharyngeal cancer from real-world data: PRO.M.E.THE.O. ACTA OTORHINOLARYNGOLOGICA ITALICA 2022; 42:205-214. [PMID: 35396587 PMCID: PMC9330744 DOI: 10.14639/0392-100x-n1672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 10/11/2021] [Indexed: 11/23/2022] [Imported: 09/01/2023]
Abstract
Objective The PRO.M.E.THE.O. study (PredictiOn Models in Ent cancer for anti-EGFR based THErapy Optimization) aimed to develop a predictive model (PM) of overall survival (OS) for patients with locally advanced oropharyngeal cancer (LAOC) treated with radiotherapy (RT) and cetuximab (Cet) from an Italian dataset. Methods We enrolled patients with LAOC from 6 centres treated with RT-Cet. Clinical and treatment variables were collected. Patients were randomly divided into training (TS) (80%) and validation (VS) (20%) sets. A binary logistic regression model was used on the TS with stepwise feature selection and then on VS. Timepoints of 2, 3 and 5 years were considered. The area under the curve (AUC) of receiver operating characteristic of 2, 3 and 5 year and confusion matrix statistics at 5-threshold were used as performance criteria. Results Overall, 218 patients were enrolled and 174 (79.8%) were analysed. Age at diagnosis, gender, ECOG performance, clinical stage, dose to high-risk volume, overall treatment time and day of RT interruption were considered in the final PMs. The PMs were developed and represented by nomograms with AUC of 0.75, 0.73 and 0.73 for TS and 0.713, 0.713, 0.775 for VS at 2, 3 and 5 years, respectively. Conclusions PRO.M.E.THE.O. allows the creation of a PM for OS in patients with LAOC treated with RT-Cet.
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Lorini L, Perri F, Vecchio S, Belgioia L, Vinches M, Brana I, Elad S, Bossi P. Confounding factors in the assessment of oral mucositis in head and neck cancer. Support Care Cancer 2022; 30:8455-8463. [PMID: 35639187 PMCID: PMC9512735 DOI: 10.1007/s00520-022-07128-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 05/09/2022] [Indexed: 11/26/2022] [Imported: 09/01/2023]
Abstract
Treatment of locally advanced head and neck carcinoma not amenable for surgical resection or resected with high-risk features is usually based on (chemo-)radiation treatment. Oral mucositis represents one of the main side effects of (chemo-)radiation, with an important impact on quality of life and causing approximately 20% of early interruption of treatment, leading to a suboptimal dose administered. Treatment and prevention of oral mucositis have a central role in the therapeutic pathways of head and neck cancer patients but remains quite challenging. Although extensive research is conducted to identify interventions for the management of mucositis, very few interventions had sufficient evidence to generate an international expert consensus. This may be partially explained by confounding factors that could influence the development and assessment of oral mucositis. Little is known about the confounding factors of oral mucositis, which, if not well balanced in an experimental study, could lead to non-solid results. The current paper aims to review the main oral mucositis confounding factors related to head and neck cancer patients.
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Intensity-Modulated Radiotherapy (IMRT) following Conservative Surgery of the Supraglottic Region: Impact on Functional Outcomes. Cancers (Basel) 2022; 14:cancers14112600. [PMID: 35681579 PMCID: PMC9179846 DOI: 10.3390/cancers14112600] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/15/2022] [Accepted: 05/20/2022] [Indexed: 02/04/2023] [Imported: 09/01/2023] Open
Abstract
Simple Summary The present study has been suggested by the previous experience of our group showing that patients treated with conventional radiotherapy (named 3D conformal radiotherapy—3D-CRT) performed after conservative surgery (CS) for tumors of the supraglottic regions experienced a high rate of severe long-term toxicity. Therefore, we reported the toxicity profile of a similar cohort of patients treated with a high-precision radiotherapy technique (named intensity-modulated radiotherapy—IMRT). Moreover, to investigate the advantage of IMRT, we performed a comparison with a historical cohort treated with 3D-CRT. Results showed that patients treated with IMRT achieved a very low toxicity profile and comparison with 3D-CRT was in favor of IMRTs. Therefore, we believe that the results of the present study provide preliminary findings on the potential of IMRT in improving the toxicity profile of patients treated with surgical organ preservation strategies for laryngeal tumors. Abstract The aim of the present study was to investigate the role of intensity-modulated radiotherapy (IMRT) on the toxicity profile of patients treated with conservative surgery (CS) of the supraglottic (SG) region. Data on patients treated with CS and postoperative radiotherapy (PORT)-IMRT were prospectively collected. Results. In total, 20 patients were analyzed. Of these, six patients (35%) required the positioning of a temporary tracheostomy. The functional larynx preservation rate was 95%. Females had a higher risk of both endoscopic intervention and chondronecrosis, while the median age was significantly higher in patients requiring enteral nutrition. The incidence of long-term severe toxicities was lower in patients treated with IMRT than in the historical 3D-CRT cohort. Patients who had received PORT-IMRT achieved a lower rate of permanent laryngeal and swallowing dysfunctions. Overall, results from the comparison with the historical 3D-CRT cohort favor the IMRTs.
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Palumbo I, Pasqualetti F, Delishaj D, Gonnelli A, Aristei C, Borghesi S, Pirtoli L, Belgioia L, Arcangeli S. Integrating stereotactic radiotherapy and systemic therapies. Rep Pract Oncol Radiother 2022; 27:310-317. [PMID: 36299395 PMCID: PMC9591045 DOI: 10.5603/rpor.a2022.0020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 01/16/2022] [Indexed: 12/03/2022] [Imported: 09/01/2023] Open
Abstract
This paper focuses on stereotactic radiotherapy (SRT ) interactions with targeted therapies and immune system modulating agents because SRT inevitably interacts with them in the treatment of oligometastatic patients. Radiation oncologists need to be aware of the advantages and risks of these interactions which can, on one hand, enhance the effect of therapy or, on the other, potentiate reciprocal toxicities. To date, few prospective studies have evaluated the interactions of SRT with new-generation drugs and data are mainly based on retrospective experiences, which are often related to small sample sizes.
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Meattini I, Livi L, Lorito N, Becherini C, Bacci M, Visani L, Fozza A, Belgioia L, Loi M, Mangoni M, Lambertini M, Morandi A. Integrating radiation therapy with targeted treatments for breast cancer: from bench to bedside. Cancer Treat Rev 2022; 108:102417. [PMID: 35623219 DOI: 10.1016/j.ctrv.2022.102417] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 05/14/2022] [Accepted: 05/17/2022] [Indexed: 11/02/2022] [Imported: 09/01/2023]
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Tagliafico AS, Rossi F, Bignotti B, Torri L, Bonsignore A, Belgioia L, Domineitto A. CT-derived relationship between low relative muscle mass and bone damage in patients with multiple myeloma undergoing stem cells transplantation. Br J Radiol 2022; 95:20210923. [PMID: 34918544 PMCID: PMC9153728 DOI: 10.1259/bjr.20210923] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] [Imported: 09/01/2023] Open
Abstract
OBJECTIVE Sarcopenia or low muscle mass is related to worse prognosis in cancer patients. We investigated whether muscle mass is related to bone damage on CT in patients with multiple myeloma (MM). METHODS Approval from the institutional review board was obtained. N = 74 consecutive patients (mean age, 60.8 years ± 9.24 [standard deviation]; range, 36-89 years) for MM who underwent transplant were included. Sarcopenia cut-off points defined as skeletal muscle index (SMI) used were<41 cm2/m2. To assess bone damage in MM the MSBDS (myeloma spine and bone damage score) was used. One-way analysis of variance and the X2 test were used. Kaplan-Meier analysis was performed to generate progression and survival curves according to SMI and MSBDS. The testing level was set at 0.05. RESULTS The median SMI was 47.1 ± 14.2 and according to SMI 18/74 (24%) had sarcopenia which was more prevalent in females (p.001). A strong and significant association between patients with low muscle mass and elevated bone damage (24/74, 32.4%) and patients with normal/non-low muscle mass low bone damage (30/74, 40.5%) was present. Multiple Logistic regression did not show any significant relationship or confounding influence among SMI and MSBDS regarding sex (p.127), cytogenetic status (p.457), staging (p.756) and relapse (.126). Neither SMI nor MSBDS resulted significantly related to overall survival as shown in Kaplan-Meier analysis. CONCLUSION Sarcopenia and bone damage affected MM patients undergoing stem cell transplantation and are significantly associated. ADVANCES IN KNOWLEDGE Quantitative measurement of sarcopenia and bone damage on CT resulted present in MM patients undergoing stem cell transplantation and are significantly associated.
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Fregatti P, Gipponi M, Atzori G, Rosa RDE, Diaz R, Cornacchia C, Sparavigna M, Garlaschi A, Belgioia L, Fozza A, Pitto F, Boni L, Blondeaux E, Depaoli F, Murelli F, Franchelli S, Zoppoli G, Lambertini M, Friedman D. The Margins' Challenge: Risk Factors of Residual Disease After Breast Conserving Surgery in Early-stage Breast Cancer. In Vivo 2022; 36:814-820. [PMID: 35241537 DOI: 10.21873/invivo.12768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 11/10/2022] [Imported: 09/01/2023]
Abstract
BACKGROUND/AIM Clinicopathological features of patients undergoing margin enlargement after lumpectomy for early breast cancer with positive/close excision margins were analyzed in order to define whether a re-operative procedure could have been avoided. Furthermore, a standardized protocol of specimen orientation was adopted in order to optimize both the widening procedure as well as the oncologic outcome. PATIENTS AND METHODS A retrospective analysis was performed including pre-, peri-, and post-operative parameters, and a predictive score by means of a multivariate model was developed using all clinically and statistically significant variables associated with residual disease (RD). RESULTS RD was significantly related to positive tumor margins, hormone receptor negative, HER2-positive, and tumors with high Ki67 proliferation index (p<0.001); the corresponding contribution to the prognostic score was as follows: close margins, 3 points; hormone receptor positive disease, 2 points; low Ki67, 2 points; HER2 negativity, 1 point. In 102 patients with a score >3, only 2 patients (2.0%) had RD, while in 81 patients with a score ≤3, 55 patients (67.9%) had RD (p<0.001). CONCLUSION This predictive model might aid in clinical-decision making of patients with positive margins who actually require a widening procedure after intraoperative and/or definitive histology.
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Efficacy of High-Ozonide Oil in Prevention of Cancer Relapses Mechanisms and Clinical Evidence. Cancers (Basel) 2022; 14:cancers14051174. [PMID: 35267482 PMCID: PMC8909345 DOI: 10.3390/cancers14051174] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/11/2022] [Accepted: 02/22/2022] [Indexed: 11/16/2022] [Imported: 09/01/2023] Open
Abstract
Background: Cancer tissue is characterized by low oxygen availability triggering neo angiogenesis and metastatisation. Accordingly, oxidation is a possible strategy for counteracting cancer progression and relapses. Previous studies used ozone gas, administered by invasive methods, both in experimental animals and clinical studies, transiently decreasing cancer growth. This study evaluated the effect of ozonized oils (administered either topically or orally) on cancer, exploring triggered molecular mechanisms. Methods: In vitro, in lung and glioblastoma cancer cells, ozonized oils having a high ozonide content suppressed cancer cell viability by triggering mitochondrial damage, intracellular calcium release, and apoptosis. In vivo, a total of 115 cancer patients (age 58 ± 14 years; 44 males, 71 females) were treated with ozonized oil as complementary therapy in addition to standard chemo/radio therapeutic regimens for up to 4 years. Results: Cancer diagnoses were brain glioblastoma, pancreas adenocarcinoma, skin epithelioma, lung cancer (small and non-small cell lung cancer), colon adenocarcinoma, breast cancer, prostate adenocarcinoma. Survival rate was significantly improved in cancer patients receiving HOO as integrative therapy as compared with those receiving standard treatment only. Conclusions: These results indicate that ozonized oils at high ozonide may represent an innovation in complementary cancer therapy worthy of further clinical studies.
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Chemo- immunotherapy and radiation in locally advanced head and neck cancer: Where do we stand? Oral Oncol 2022; 127:105773. [PMID: 35217401 DOI: 10.1016/j.oraloncology.2022.105773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/20/2022] [Accepted: 02/13/2022] [Indexed: 11/21/2022] [Imported: 09/01/2023]
Abstract
Immunotherapy represents an effective therapeutic option in the management of recurrent/metastatic head and neck squamous cell carcinoma, along with chemotherapy in metastatic disease or radiotherapy/re-irradiation for (locoregionally confined) recurrent disease. On the other hand, concomitant chemo-radiation remains the primary treatment modality in many patients with locally advanced disease. In spite of promising preclinical, it is difficult to clearly establish the role of immunotherapy in the upfront management of locally advanced head and neck squamous cell carcinoma and its integration with the standard of care. In this paper, we discuss/review the main results thus far available and outline some unanswered questions that might help design future clinical trials.
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De Felice F, Crocetti D, Petrucciani N, Belgioia L, Sapienza P, Bulzonetti N, Marampon F, Musio D, Tombolini V. Treatment in locally advanced rectal cancer: a machine learning bibliometric analysis. Therap Adv Gastroenterol 2021; 14:17562848211042170. [PMID: 34671421 PMCID: PMC8521411 DOI: 10.1177/17562848211042170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 07/27/2021] [Indexed: 02/04/2023] [Imported: 09/01/2023] Open
Abstract
A bibliometric analysis was performed using a machine learning bibliometric methodology in order to evaluate the research trends in locally advanced rectal cancer treatment between 2000 and 2020. Information regarding publication outputs, countries, institutions, journals, keywords, funding, and citation counts was retrieved from Scopus database. During the search process, a total of 2370 publications were identified. The vast majority of papers originated from the United States of America, reflecting also its research drive in the collaboration network. Neoadjuvant treatment was the topic most studied in the highly cited studies. New keywords, including neoadjuvant chemotherapy, multiparametric magnetic resonance imaging, circulating tumor DNA, and genetic heterogeneity, appeared in the last 2 years. The quantity of publications on locally advanced rectal cancer treatment since 2000 showed an evolving research field. The 'new' keywords explain where research is presently heading.
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Prognostic value of high-risk human papillomavirus DNA and p16 INK4a immunohistochemistry in patients with anal cancer: An individual patient data meta-analysis. Eur J Cancer 2021; 157:165-178. [PMID: 34517306 DOI: 10.1016/j.ejca.2021.07.041] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 07/22/2021] [Accepted: 07/26/2021] [Indexed: 12/24/2022] [Imported: 09/01/2023]
Abstract
BACKGROUND High-risk human papillomavirus (hrHPV) types represent the aetiological agents in a major proportion of anal squamous cell carcinomas (ASCC). Several studies have suggested a prognostic relevance of HPV-related markers, particularly hrHPV DNA and p16INK4a (p16) protein expression, in patients with ASCC. However, broader evaluation of these prognostic marker candidates has been hampered by small cohort sizes and heterogeneous survival data among the individual studies. We conducted an individual patient data (IPD) meta-analysis to determine the prognostic value of hrHPV DNA and p16 in patients with ASCC while controlling for major clinical and tumour covariates. PATIENTS AND METHODS A systematic literature search was conducted to identify all published studies analysing p16 alone or in combination with hrHPV DNA and reporting survival data in patients with ASCC. Clinical and tumour-related IPD were requested from authors of potentially eligible studies. Survival analyses were performed with a proportional hazard Cox model stratified by study and adjusted for relevant covariates. The study-specific hazard ratios (HRs) for the exposures were pooled using a random-effects model. Kaplan-Meier curves from different studies were pooled per exposure group and weighted by the study's total sample size. RESULTS Seven studies providing IPD from 693 patients with ASCC could be included in the meta-analysis. Seventy-six percent of patients were p16+/hrHPV DNA+, whereas 11% were negative for both markers. A discordant marker status was observed in 13% of cases. Patients with p16+/hrHPV DNA+ ASCC showed significantly superior overall survival (OS) compared with patients with p16-/hrHPV DNA- tumours (pooled adjusted HR = 0.26 [95% confidence interval {CI}, 0.14-0.50]) with pooled three-year OS rates of 86% (95% CI, 82-90%) versus 39% (95% CI, 24-54%). Patients with discordant p16 and hrHPV DNA status showed intermediate three-year OS rates (75% [95% CI, 56-86%] for p16+/hrHPV DNA- and 55% [95% CI, 35-71%] for p16-/hrHPV DNA+ ASCC). CONCLUSION This first IPD meta-analysis controlling for confounding variables shows that patients with p16+/hrHPV DNA+ ASCC have a significantly better survival than patients with p16-/hrHPV DNA- tumours.
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Belgioia L, Fozza A, Trapani L, Carmisciano L, Cavagnetto F, Agostinelli S, Guenzi M, Friedman D, Fregatti P, Corvò R. Ten Daily Fractions for Whole Breast Cancer Irradiation: Long Term Results. In Vivo 2021; 35:2875-2880. [PMID: 34410981 PMCID: PMC8408691 DOI: 10.21873/invivo.12576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/09/2021] [Accepted: 06/16/2021] [Indexed: 11/10/2022] [Imported: 08/29/2023]
Abstract
BACKGROUND/AIM To report the feasibility and oncological outcomes in breast cancer patients treated with a short hypofractionated radiotherapy schedule. PATIENTS AND METHODS We evaluated 380 breast cancer patients treated with ten daily fractions of radiotherapy up to 39 Gy on tumor bed. Primary endpoint was local relapse rate (LRR). Secondary endpoints were overall survival (OS) and metastasis-free survival (MFS). RESULTS The median follow up was 5.0 years. Two- and 5-year LRR rates were 0.2 and 2%, respectively. Two- and 5-year MFS rates were 96.1% and 90.5%, respectively. Two and 5-year OS rates were 97.4% and 95%, respectively. CONCLUSION This short schedule may represent an alternative option to standard mild hypofractionated radiotherapy in breast cancer patients due to its excellent feasibility and very low recurrence rate.
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Desideri I, Becherini C, Belgioia L, Merlotti A, Ciccone LP, Franzese C, Loi M, De Felice F, Mazzola R, Caini S, Livi L, Bonomo P. Palliative radiotherapy in older adults with head and neck squamous cell carcinoma: A systematic review. Oral Oncol 2021; 119:105355. [PMID: 34044315 DOI: 10.1016/j.oraloncology.2021.105355] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 04/26/2021] [Accepted: 05/16/2021] [Indexed: 11/30/2022] [Imported: 09/01/2023]
Abstract
Locally advanced Head and neck squamous cell carcinoma (SCCHN) represents a common oncologic pathology in older adults (OA). While radiotherapy represents a cornerstone in this context, it is unclear what is the optimal radiation regimen for SCCHN in the palliative setting, especially for OA. This article addresses issues related to palliative radiotherapy (PRT) in this setting with a focus on treatment modalities and toxicity. We also explore the use of quality of life and geriatric assessment in this setting. Medline, Scopus and Embase databases were queried for articles in this setting. We included studies published from January 1, 2000 through June 1, 2020, that were independently evaluated by two authors. Analyzed endpoints were progression free survival (PFS), overall survival (OS) and PRT toxicities. The meta-analysis was performed using Stata v.14. A total of 33 studies were included in this meta-analysis. The pooled median OS is 7.7 months, 2-years OS was worse for higher radiation dose (p = 0.02). The pooled median PFS was 5.4 months, PFS was influenced by EQD2 (p = 0.01), with patients receiving an EQD2 < 40 Gy that presented a poorer outcome. Regarding acute toxicities, most common pooled G3 toxicities were mucositis (7%) and dysphagia (15%). Among late toxicity, most common G3 toxicity was dysphagia in 7% of patients. Radiotherapy should be the most effective palliative treatment in symptomatic SCCHN OA. A tailored approach, guided by geriatric tools, would be indicated to choose the right therapy.
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Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28- T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer. Cancers (Basel) 2021; 13:cancers13092234. [PMID: 34066538 PMCID: PMC8124419 DOI: 10.3390/cancers13092234] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 04/13/2021] [Accepted: 04/27/2021] [Indexed: 12/21/2022] [Imported: 09/01/2023] Open
Abstract
Simple Summary CD8+ T lymphocytes are among the immune cells reputed to kill tumor cells. Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of infiltrating CD8+ T cells in a cohort of 30 HNSCC patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28− T cells, and CD8+CD28−CD127−CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, we identified an intratumoral CD8+CD28- T cell subpopulation, which expressed markers of both exhausted (i.e., with impaired effector functions) and regulatory (i.e., exerting suppressive activities) cells. This suggests that in HNSCC effector T cells progressively undergo exhaustion and acquisition of regulatory properties, hampering their anti-tumor functions. Abstract Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate in the majority of patients. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of HNSCC infiltrating CD8+ T cells in a cohort of 30 patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28− T cells, and CD8+CD28−CD127−CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, high PD1 expression identified a CD8+CD28− T cell subpopulation, phenotypically/functionally corresponding to CD8+CD28−CD127−CD39+ Treg, which showed a high expression of markers of exhaustion. This observation suggests that development of exhaustion and acquisition of regulatory properties may configure the late differentiation stage for intratumoral effector T cells, a phenomenon we define as effector-to-regulatory T cell transition.
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