Lena Specht

Radiotherapy for early-stage Hodgkin lymphoma (HL) has undergone substantial transformation over the last several decades, from being the sole treatment modality using large treatment fields to adjuvant local therapy directed to limited site(s) after systemic therapy. Radiation doses and field sizes have decreased, leading to dramatic reductions in risks of long-term complications from radiotherapy compared with the treatments of the past. Meta-analysis of randomized trials of chemotherapy with or without radiotherapy show a highly significant advantage for inclusion of radiotherapy both with regard to tumor control and with regard to overall survival (OS). There is as yet no documented method to select patients for treatment without radiotherapy, not even by positron emission tomography (PET) response. The treatment of choice for early-stage HL is abbreviated chemotherapy followed by limited radiation therapy. Continued advances in radiation therapy technology will further improve targeting while sparing normal tissues.

During the past 4 decades, the treatment of Hodgkin lymphoma has changed dramatically, and combined modality treatment is now considered the standard of care for patients with early-stage disease. However, the risk of late effects has led to concerns regarding the use of radiation therapy, especially in young patients with a long life expectancy. In this study, we review the current evidence for modern radiation therapy planning and delivery techniques in the treatment of early-stage Hodgkin lymphoma with a focus on a reduced delivered dose, a reduced irradiated volume, and a more conformal dose distribution. Although studies are difficult to compare because of differences in field technique, prescribed dose, target volumes, patient population, and reported dosimetric and plan evaluation parameters, modern radiation therapy significantly reduces exposure to normal tissues and thereby the estimated risk of late effects. However, there is no such thing as a single best modern delivery...

Radiotherapy for cancer previously employed large treatment fields whereby cures were obtained. However, long-term follow-up documented serious long-term complications due to irradiation of normal tissues. Modern technology makes it possible to very accurately shape the high-dose volume. However, new problems emerge. Organ movement must be managed and the precise definition of the extent of the tumour tissue is crucial. Positron emission tomography and magnetic resonance imaging are increasingly used. Biological imaging may enable us to image tumour biology more accurately and modify radiation doses accordingly.

To assess the effect of more extensive radiotherapy and of adjuvant combination chemotherapy on long-term outcome of early-stage Hodgkin's disease. In a collaborative worldwide systematic overview, individual patient data were centrally reviewed on 1,974 patients in eight randomized trials of more versus less extensive radiotherapy and on 1,688 patients in 13 trials of radiotherapy plus chemotherapy versus radiotherapy alone. Crude mortality data on 226 patients in two other trials of chemotherapy were also reviewed. More extensive radiotherapy reduced the risk of treatment failure (resistant or recurrent disease) at 10 years by more than one third (31.3% v 43.4% failures; P < .00001), but there was no apparent improvement in overall 10-year survival (77.1 % v 77.0% alive). The addition of chemotherapy to radiotherapy halved the 10-year risk of failure (15.8% v 32.7%; P < .00001), with a small, nonsignificant improvement in survival (79.4% v 76.5% alive). This involved a r...

In early stage Hodgkin's disease the optimal choice of treatment is still an unresolved issue. Twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out world-wide. The preliminary results of a global meta-analysis of these trials indicate that we still do not definitively know whether or not the early addition of prophylactic chemotherapy improves survival. Arguments in favour of early chemotherapy are: that laparotomy may be avoided, that radiation fields and doses may perhaps be reduced, and that the stress of experiencing a relapse is avoided in many patients. The major argument against early chemotherapy is: that by careful staging and selection of patients and by careful radiotherapy techniques the number of patients exposed to potentially toxic chemotherapy may be kept at a minimum. Recently, trials have been carried out testing chemotherapy alone, results are, however, conflicting. In order not to jeopardiz...

47 patients with advanced Hodgkin's disease (stage IIIB or IV) and mediastinal involvement, treated during the period 1969-78 and followed till death or from 36 to 126 months after initiation of therapy, were analysed. All 47 patients had received combination chemotherapy (MOPP or equivalent regimens). 20 had also received additional radiotherapy to mediastinum (and in some cases to other involved areas as well). The 2 treatment groups did not differ significantly with regard to the more important prognostic factors. Both in the case of stages IV and IIIB patients in the group treated with combination chemotherapy alone, remissions were significantly more often only partial, the frequency of relapse and of treatment failure was significantly higher, and relapse-free survival was significantly poorer than in the group treated with additional radiotherapy. Furthermore, survival from Hodgkin's disease and crude survival including all causes of death were significantly better fo...

94 patients with Hodgkin's disease PS I or II, treated during the period 1969-78 and followed until death, or from 33 to 136 months after initiation of therapy, were analysed. 47 patients had been treated with radiotherapy alone (mantle field irradiation and, in all but 12 cases, irradiation of infradiaphragmatic lymph nodes), while the other 47 had been treated with mantle field irradiation plus 6 cycles of combination chemotherapy (MOPP or an equivalent regimen). Of the patients treated with radiotherapy alone, 13 relapsed whereas only 1 of the patients treated with radiotherapy plus combination chemotherapy relapsed. The initial tumour burden of each patient was estimated, combining tumour size of each involved area and number of sites involved. For patients treated with radiotherapy alone, a large tumour burden singled out the patients destined to relapse more accurately than other prognostic factors including pathological stage, B-symptoms, mediastinal involvement, bulky me...

Second malignancies (SM) are a major late effect of treatment for Hodgkin's disease (HD). Reliable comparisons of SM risk between alternative treatment strategies are lacking. Radiotherapy (RT), chemotherapy (CT) and combined chemo-radiotherapy (CRT) for newly-diagnosed Hodgkin's disease are compared with respect to SM risk, overall (OS) and progression-free (PFS) survival. Further, involved-field (IF-)RT is compared to extended-field (EF-)RT. We searched the Cochrane Controlled Trials Register, PubMed, EMBASE, CancerLit, LILACS, relevant conference proceedings, trials lists and publications. RCTs accruing 30+ patients and completing accrual before/during 2000, comparing at least two treatment modalities for newly-diagnosed HD. Individual patient data were collected and assessed for data quality. Trialists submitted additional information concerning methods and data quality. Peto Odds Ratios (OR) with 95% confidence intervals (CI) were calculated for OS, PFS and SM-free survival. Secondary acute leukemia (AL), non-Hodgkin's lymphoma (NHL) and solid tumours (ST) were also analysed separately. 37 trials (9312 patients) were analysed: 15 (3343) for RT vs. CRT, 16 (2861) for CT vs. CRT, 3 (415) for RT vs. CT and 10 (3221) for IF-RT vs. EF-RT.CRT was superior to RT in terms of OS (OR=0.76, CI=0.66 to 0.89, p=0.0004), PFS (OR=0.49, CI=0.43 to 0.56, p<0.0001) and SM (OR=0.78. CI=0.62 to 0.98, p=0.03). The superiority of CRT also applied to early and advanced stages (mainly IIIA) separately. Excess SM with RT is due mainly to ST and is apparently caused by greater need for salvage therapy after RT.CRT was superior to CT in terms of PFS (OR=77, CI 0.68 to 0.77, p<0.0001). OS was better with CRT for early stages only (OR=0.62, CI 0.44 to 0.88, p=0.006). SM risk was higher with CRT (OR=1.38, CI 1.00 to 1.89, p=0.05), although not significant for early stages alone. This effect, also seen in AL and ST separately, was due directly to first-line treatment. Data were insufficient to compare RT to CT.EF-RT was superior to IF-RT (each additional to CT in most trials) in terms of PFS (OR=81, CI 0.68 to 0.95, p=0.009) but not OS. No significant difference in SM was observed. CRT seems to be optimal for most early stage (I-II) HD patients. For advanced stages (III-IV), CRT better prevents progression/relapse but CT alone seems to cause less SM. RT alone gives a higher overall SM risk than CRT due to increased need for salvage therapy. Reduced SM risk after IF-RT instead of EF-RT could not be demonstrated. Due to the large number of studies excluded because no IPD were received, to the inclusion of many outdated treatments and to the limited amount of long-term data, one must be cautious in applying these results to current therapies.