Bernhard Berger

Reduced Treatment Intensity in Patients with Early-Stage Hodgkin's Lymphoma

BACKGROUND Whether it is possible to reduce the intensity of treatment in early (stage I or II) Hodgkins lymphoma with a favorable prognosis remains unclear. We therefore conducted a multicenter, randomized trial comparing four treatment groups consisting of a combination chemotherapy regimen of two different intensities followed by involved-field radiation therapy at two different dose levels. METHODS We randomly assigned 1370 patients with newly diagnosed early-stage Hodgkins lymphoma with a favorable prognosis to one of four treatment groups: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of radiation therapy (group 1), four cycles of ABVD followed by 20 Gy of radiation therapy (group 2), two cycles of ABVD followed by 30 Gy of radiation therapy (group 3), or two cycles of ABVD followed by 20 Gy of radiation therapy (group 4). The primary end point was freedom from treatment failure; secondary end points included efficacy and toxicity of treatment. RESULTS The two chemotherapy regimens did not differ significantly with respect to freedom from treatment failure (P=0.39) or overall survival (P=0.61). At 5 years, the rates of freedom from treatment failure were 93.0% (95% confidence interval [CI], 90.5 to 94.8) with the four-cycle ABVD regimen and 91.1% (95% CI, 88.3 to 93.2) with the two-cycle regimen. When the effects of 20-Gy and 30-Gy doses of radiation therapy were compared, there were also no significant differences in freedom from treatment failure (P=1.00) or overall survival (P=0.61). Adverse events and acute toxic effects of treatment were most common in the patients who received four cycles of ABVD and 30 Gy of radiation therapy (group 1). CONCLUSIONS In patients with early-stage Hodgkins lymphoma and a favorable prognosis, treatment with two cycles of ABVD followed by 20 Gy of involved-field radiation therapy is as effective as, and less toxic than, four cycles of ABVD followed by 30 Gy of involved-field radiation therapy. Long-term effects of these treatments have not yet been fully assessed. (Funded by the Deutsche Krebshilfe and the Swiss Federal Government; ClinicalTrials.gov number, NCT00265018.)

High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: Results of a survey in EORTC institutes

OBJECTIVE Examination of the rate of grade III or grade IV radiation dermatitis during treatment of head and neck cancer (HNC) with radiotherapy (RT) and concurrent cetuximab in EORTC centres. MATERIALS AND METHOD A questionnaire was sent to all members of the EORTC Radiation Oncology Group and Head and Neck Group (111 institutions) to evaluate the widespread use of cetuximab and radiotherapy in HNC and to estimate the frequency of grades III and IV skin reactions in the radiation portals associated with this protocol. Co-morbidities, RT schedules and co-medications were also recorded. RESULTS We received responses from 28 institutions in 11 countries. A total of 125 HNC patients from 15 institutions were treated with cetuximab and concurrent RT. Information about the skin reactions was available from 71 patients. Of these 36 had no grade III/IV adverse effects in the RT field, 15 had a grade III and 20 had grade IV radiation dermatitis. No detectable relation of grades III and IV radiation dermatitis with co-morbidities such as liver insufficiency or renal dysfunction was found. CONCLUSION According to the results of the questionnaire, grade III/IV radiation dermatitis is observed in 49% of HNC patients treated with cetuximab and concurrent RT. A systematic clinical monitoring of cutaneous side effects during RT plus cetuximab is advised to ensure the safety of this protocol.

EGFr inhibitor toxicityHigh rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: Results of a survey in EORTC institutes

OBJECTIVE Examination of the rate of grade III or grade IV radiation dermatitis during treatment of head and neck cancer (HNC) with radiotherapy (RT) and concurrent cetuximab in EORTC centres. MATERIALS AND METHOD A questionnaire was sent to all members of the EORTC Radiation Oncology Group and Head and Neck Group (111 institutions) to evaluate the widespread use of cetuximab and radiotherapy in HNC and to estimate the frequency of grades III and IV skin reactions in the radiation portals associated with this protocol. Co-morbidities, RT schedules and co-medications were also recorded. RESULTS We received responses from 28 institutions in 11 countries. A total of 125 HNC patients from 15 institutions were treated with cetuximab and concurrent RT. Information about the skin reactions was available from 71 patients. Of these 36 had no grade III/IV adverse effects in the RT field, 15 had a grade III and 20 had grade IV radiation dermatitis. No detectable relation of grades III and IV radiation dermatitis with co-morbidities such as liver insufficiency or renal dysfunction was found. CONCLUSION According to the results of the questionnaire, grade III/IV radiation dermatitis is observed in 49% of HNC patients treated with cetuximab and concurrent RT. A systematic clinical monitoring of cutaneous side effects during RT plus cetuximab is advised to ensure the safety of this protocol.

Evidence-based radiation oncology: Oesophagus

Oesophageal cancer remains to be a therapeutic and diagnostic challenge in multidisciplinary oncology. Radiotherapy is a crucial component of most curative and palliative approaches for oesophageal cancer. Aim of this educational review is to summarize the available evidence and to define the role of radiation-based treatment options for oesophageal cancer.

RADIATION THERAPY FOR TREATMENT OF PIGMENTED VILLONODULAR SYNOVITIS: RESULTS OF A NATIONAL PATTERNS OF CARE STUDY

PURPOSE The German Cooperative Group on Radiotherapy in Benign Diseases (GCG-BD) conducted a pattern-of-care study (PCS) to analyze the radiation therapy (RT) practice for pigmented villonodular synovitis (PVNS). METHODS AND MATERIALS In 2007, a structured questionnaire to assess the number of patients, the pretreatments, the RT indication, technique, target volume concepts, outcome data, and possible early or late toxicity was circulated to 227 institutions. RESULTS Until August 2008, a response was available from 189 institutions (83.2 %), of whom 19 (10.0 %) experienced RT for PVNS. Complete clinical information was available for 41 patients from 14 RT departments. Thirty patients (73.2 %) received postsurgical RT because of primary incomplete resection, 11 patients (26.8 %) as an adjunct after complete resections of recurrences or unclear resection status. The total doses ranged from 30 to 50 Gy (median, 36 Gy), the median single dose was 2.0 Gy. Local control was achieved 95.1%, and 82.9% had no or only slight functional impairment. The early and late toxicity was mild (<or=RTOG Grade II). CONCLUSIONS Radiation therapy is a safe and effective treatment for PVNS in the postoperative setting after incomplete resection, and also as a salvage option for treatment of recurrences it provides a high rate of local control.

Severe skin reaction secondary to concomitant radiotherapy plus cetuximab

The therapeutic use of monoclonal antibodies against the epidermal growth factor receptor (EGFR) is specifically associated with dermatologic reactions of variable severity. Recent evidence suggests superiority of the EGFR inhibitor (EGFRI) cetuximab plus radiotherapy compared to radiotherapy alone in patients with squamous cell carcinoma of the head and neck. Although not documented in a study population, several reports indicate a possible overlap between radiation dermatitis and the EGFRI-induced skin rash. We here present a case of severe skin reaction secondary to the addition of cetuximab to radiotherapy.

Radiation Therapy for Gorham-Stout Syndrome: Results of a National Patterns-of-Care Study and Literature Review

PURPOSE The German Cooperative Group on Radiotherapy for Benign Diseases conducted a national patterns-of-care study to investigate the value of radiation therapy (RT) in the management of Gorham-Stout syndrome. METHODS AND MATERIALS In 2009 a structured questionnaire was circulated to 230 German RT institutions to assess information about the number of patients, the RT indication and technique, and the target volume definition, as well as accompanying treatments, outcome data, and early or late radiation toxicity. RESULTS In November 2009 responses were available from 197 departments (85.6%): 29 university hospitals (14.7%), 89 community hospitals (45.2%), and 79 private RT offices (40.1%). Of these institutions, 8 (4.0%) had experience using RT, for a total of 10 cases in various anatomic sites. Four patients underwent irradiation postoperatively, and six patients received primary RT. The total doses applied after computed tomography-based treatment planning ranged from 30 to 45 Gy. After a median follow-up period of 42 months, local disease progression was avoided in 8 cases (80.0%). In 2 of these cases a progression occurred beyond the target volume. Acute and late toxicity was mild; in 4 patients RT was associated with Grade I side effects according to Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. The literature analysis of 38 previously published articles providing results after the use of RT in 44 patients showed stable or regressive disease in 77.3%. CONCLUSIONS RT may prevent disease progression effectively in Gorham-Stout syndrome in 77% to 80% of cases. Total doses ranging from 30 to 45 Gy applied after computed tomography-based treatment planning are recommended.

Reirradiation with Alternating Docetaxel-Based Chemotherapy for Recurrent Head and Neck Squamous Cell Carcinoma

Purpose:To report follow-up data and results of a dose escalation within a prospective phase II protocol scheduling alternating chemoreirradiation for patients with unresectable locoregional recurrence of head and neck cancer after previous curative-intent radiotherapy.Patients and Methods:Chemoreirradiation was initially performed in 27 patients by 40.0 Gy split-course reirradiation (re-RT) alternating with three cycles of docetaxel 50 mg/m2 day 1 and cisplatin 15 mg/m2 days 2–5 (first cohort). From 2002 onward, 30 consecutively treated patients received a late-course concomitant boost to 49.6 Gy (second cohort). In July 2008, the survival outcome was analyzed separately for both cohorts and the entire collective (n = 57).Results:The Kaplan-Meier estimates for 1- and 2-year overall survival (OS) were 52% and 24%, respectively (median OS 13.4 months). The median time of locoregional control was 9.6 months, and the actuarial 2-year freedom from distant metastasis rate was 55%. The re-RT dose escalation led to a significant improvement of the median OS (17.4 vs. 9.4 months; p = 0.039). Irrespective of the cohort, severe treatment-related toxicities occurred in about one third of patients.Conclusion:The treatment results confirm the efficacy and the safety of escalated re-RT doses in this chemoreirradiation protocol.ZusammenfassungZiel:Berichtet werden das Follow-up einer Phase-II-Studie zur alternierenden Reradiochemotherapie lokoregional rezidivierender, inoperabler HNO-Plattenepithelkarzinome sowie die Auswirkungen der in ihrem Rahmen erfolgten Dosiseskalation.Patienten und Methodik:Das ursprüngliche Therapieprotokoll umfasste drei Zyklen Chemotherapie (Docetaxel 50 mg/m2 Tag 1, Cisplatin 15 mg/m2 Tage 2–5) in den Wochen 1, 5 und 7, alternierend mit einer „split-course“-Rebestrahlung bis 40,0 Gy (täglich 2,0 Gy in den Wochen 2 + 3 und 5 + 6). Nach einer Zwischenauswertung im Jahr 2002 (erste Kohorte, n = 27) erhielten weitere 30 Patienten (zweite Kohorte) in Woche 6 einen konkomitanten Boost bis 49,6 Gy. Im Juli 2008 wurden die Studienendpunkte separat für beide Kohorten sowie für das Gesamtkollektiv (n = 57) analysiert.Ergebnisse:Im Gesamtkollektiv betrugen das 1- und 2-Jahres-Überleben 52% und 24% (medianes Überleben 13,4 Monate). Die mediane lokoregionale Kontrolle lag bei 9,6 Monaten, und nach 2 Jahren waren 55% der Patienten metastasenfrei. Die Dosiseskalation in der zweiten Kohorte führte zu einem signifikant verbesserten Gesamtüberleben (17,4 vs. 9,4 Monate; p = 0,039). Etwa ein Drittel der Patienten erlitt schwere behandlungsassoziierte Toxizitäten, und dies war unabhängig von der Patientenkohorte.Schlussfolgerung:Die Behandlungsergebnisse bestätigen die Effektivität und Sicherheit einer Dosiseskalation im Rahmen dieses Therapieprotokolls.

Reirradiation with alternating docetaxel-based chemotherapy for recurrent head and neck squamous cell carcinoma: update of a single-center prospective phase II protocol.

Purpose:To report follow-up data and results of a dose escalation within a prospective phase II protocol scheduling alternating chemoreirradiation for patients with unresectable locoregional recurrence of head and neck cancer after previous curative-intent radiotherapy.Patients and Methods:Chemoreirradiation was initially performed in 27 patients by 40.0 Gy split-course reirradiation (re-RT) alternating with three cycles of docetaxel 50 mg/m2 day 1 and cisplatin 15 mg/m2 days 2–5 (first cohort). From 2002 onward, 30 consecutively treated patients received a late-course concomitant boost to 49.6 Gy (second cohort). In July 2008, the survival outcome was analyzed separately for both cohorts and the entire collective (n = 57).Results:The Kaplan-Meier estimates for 1- and 2-year overall survival (OS) were 52% and 24%, respectively (median OS 13.4 months). The median time of locoregional control was 9.6 months, and the actuarial 2-year freedom from distant metastasis rate was 55%. The re-RT dose escalation led to a significant improvement of the median OS (17.4 vs. 9.4 months; p = 0.039). Irrespective of the cohort, severe treatment-related toxicities occurred in about one third of patients.Conclusion:The treatment results confirm the efficacy and the safety of escalated re-RT doses in this chemoreirradiation protocol.ZusammenfassungZiel:Berichtet werden das Follow-up einer Phase-II-Studie zur alternierenden Reradiochemotherapie lokoregional rezidivierender, inoperabler HNO-Plattenepithelkarzinome sowie die Auswirkungen der in ihrem Rahmen erfolgten Dosiseskalation.Patienten und Methodik:Das ursprüngliche Therapieprotokoll umfasste drei Zyklen Chemotherapie (Docetaxel 50 mg/m2 Tag 1, Cisplatin 15 mg/m2 Tage 2–5) in den Wochen 1, 5 und 7, alternierend mit einer „split-course“-Rebestrahlung bis 40,0 Gy (täglich 2,0 Gy in den Wochen 2 + 3 und 5 + 6). Nach einer Zwischenauswertung im Jahr 2002 (erste Kohorte, n = 27) erhielten weitere 30 Patienten (zweite Kohorte) in Woche 6 einen konkomitanten Boost bis 49,6 Gy. Im Juli 2008 wurden die Studienendpunkte separat für beide Kohorten sowie für das Gesamtkollektiv (n = 57) analysiert.Ergebnisse:Im Gesamtkollektiv betrugen das 1- und 2-Jahres-Überleben 52% und 24% (medianes Überleben 13,4 Monate). Die mediane lokoregionale Kontrolle lag bei 9,6 Monaten, und nach 2 Jahren waren 55% der Patienten metastasenfrei. Die Dosiseskalation in der zweiten Kohorte führte zu einem signifikant verbesserten Gesamtüberleben (17,4 vs. 9,4 Monate; p = 0,039). Etwa ein Drittel der Patienten erlitt schwere behandlungsassoziierte Toxizitäten, und dies war unabhängig von der Patientenkohorte.Schlussfolgerung:Die Behandlungsergebnisse bestätigen die Effektivität und Sicherheit einer Dosiseskalation im Rahmen dieses Therapieprotokolls.

Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone

Purpose: To evaluate the influence of regional hyperthermia on rates of complete pathological response (pCR) and sphincter-sparing surgery in the context of an up-to-date radiochemotherapy protocol for locally advanced rectal cancer. Methods: Between 2007 and 2010, 106 patients with locally advanced cancer of the middle and lower rectum were admitted to neoadjuvant radiochemotherapy either with (n = 61) or without (n = 45) regional hyperthermia. A retrospective comparison was performed between two groups: 45 patients received standard treatment consisting of 5040 cGy in 28 fractions to the pelvis and 5-fluorouracil (RCT group) and 61 patients received the same treatment in combination with regional hyperthermia (HRCT group). Target temperature was 40.5°C for at least 60 min. Total mesorectal excision was performed routinely. Results: pCR was seen in 6.7% of patients in the RCT group and 16.4% in the HRCT group. Patients who received at least four hyperthermia treatments (n = 40) achieved a significantly higher pCR rate (22.5%) than the remaining 66 patients (p = 0.043). Rates of sphincter-sparing surgery were similar in both groups with 64% in the RCT group and 66% in HRCT. When considering only low-lying tumours located within 8 cm of the anal verge prior to treatment, the rate of sphincter-sparing surgery was 57% in the HRCT group compared with 35% in the RCT group (p = 0.077). Conclusion: The combination of regional hyperthermia and neoadjuvant radiochemotherapy may lead to an increased pCR rate in locally advanced rectal cancer. Patients with low-lying tumours especially may benefit when additional downsizing allows sphincter-preserving surgery.