Prognostic impact of human papillomavirus status, survivin, and epidermal growth factor receptor expression on survival in patients treated with radiochemotherapy for very advanced nonresectable oropharyngeal cancer.

BACKGROUND: The influence of human papillomavirus (HPV) status on survival for patients with very advanced inoperable oropharyngeal SCC treated with radiochemotherapy (RCT) was studied. METHODS: Patients received either 69.2 Gy with concomitant boost (ccb) or 70 Gy conventionally fractionated (cf), weekly paclitaxel 40 mg/m(2), and carboplatin area under the concentration-time curve (AUC) 1. Tumor was analyzed for the presence of high-risk HPV-DNA using polymerase chain reaction (PCR) and direct DNA sequencing. p16-expression, survivin, and epidermal growth factor receptor (EGFR) expression were evaluated by immunohistochemistry and influence on survival was calculated. RESULTS: Of 52 patients, 25.0% were HPV positive and 75.0% HPV negative. The 2-year progression-free survival (PFS) was 70.1% for p16-positive patients and 37.1% for p16-negative patients (p = .005). The 3-year overall survival (OS) rate was 43.9% for all patients and did not significantly differ between the groups. Neither survivin nor EGFR expression influenced PFS or OS significantly. CONCLUSIONS: HPV status influences PFS in patients with advanced, nonresectable tumor stages but not OS. Additional risk factors seem to have a stronger influence on survival than HPV status.

Intracranial ependymoma: long-term results in a series of 21 patients treated with stereotactic (125)iodine brachytherapy.

BACKGROUND: We evaluated the long-term outcome in patients harboring intracranial ependymomas treated with interstitial brachytherapy (IBT). METHODS: Twenty-one patients (M/F = 9/12; median age: 29 years; range: 8-70 years), diagnosed with intracranial ependymoma (1 WHO I, 11 WHO II, 9 WHO III) were treated with IBT using stereotactically implanted (125)Iodine seeds between 1987 and 2010, either primarily, as adjuvant therapy following incomplete resection, or as salvage treatment upon tumor recurrence. Sixteen of 21 patients underwent microsurgical resection prior to IBT; in 5 patients, IBT was performed primarily after stereotactic biopsy for histological diagnosis. The cumulative tumor surface dose ranged from 50-65 Gy treating a median tumor volume of 3.6 ml (range, 0.3-11.6 ml). A median follow-up period of 105.3 months (range, 12.7-286.2 months) was evaluated. RESULTS: Actuarial 2-, 5- and 10-years overall- and disease-specific survival rates after IBT were each 90% and 100% at all times for ependymomas WHO I/II, for anaplastic ependymomas WHO III 100%, 100%, 70% and 100%, 100%, 86%, respectively. The neurological status of seven patients improved, while there was no change in 12 and deterioration in 2 patients, respectively. Follow-up MR images disclosed a complete tumor remission in 3, a partial remission in 12 and a stable disease in 6 patients. Treatment-associated morbidity only occurred in a single patient. CONCLUSIONS: This study shows that stereotactic IBT for intracranial ependymomas is safe and can provide a high degree of local tumor control. Due to the low rate of side effects, IBT may evolve into an attractive alternative to microsurgery in ependymomas located in eloquent areas or as a salvage treatment.

Radiotherapy for giant cell tumors of the bone: a safe and effective treatment modality.

BACKGROUND: Giant cell tumor of the bone (GCTB) is a benign or sometimes semi-malignant neoplasm accounting for 5% of all primary bone tumors. This type of tumor has been historically considered as radioresistant, but nowadays radiotherapy (RT) is used in unresectable, recurrent or incompletely resected cases. Since the value of RT is not well defined, a national cohort study was conducted. PATIENTS AND METHODS: Six German institutions collected data from 35 patients treated during the last 35 years and analyzed them. RESULTS: From 1975-2010 16 male and 19 female patients with 39 lesions were irradiated for GCTB. The median age was 30 years and the median follow-up 65 months. Nineteen patients had undergone RT for recurrent or unresectable disease and 16 patients for non-in-sano resection. The actuarial 5-year overall and disease-free survival rates were 90% and 59%, respectively. CONCLUSION: RT is an easy, safe and effective method for the treatment of GCTB. It may provide an attractive alternative to mutilating surgery.

Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial.

BACKGROUND: The intensity of chemotherapy and need for additional radiotherapy in patients with advanced stage Hodgkin's lymphoma has been unclear. We did a prospective randomised clinical trial comparing two reduced-intensity chemotherapy variants with our previous standard regimen. Chemotherapy was followed by PET-guided radiotherapy. METHODS: In this parallel group, open-label, multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed advanced stage Hodgkin's lymphoma aged 18-60 years were randomly assigned to receive either eight cycles of BEACOPP(escalated) (8×B(esc) group), six cycles of BEACOPP(escalated) (6×B(esc) group), or eight cycles of BEACOPP(14) (8×B(14) group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non-inferiority of the primary endpoint, freedom from treatment failure, was assessed using repeated CIs for the hazard ratio (HR) according to the intention-to-treat principle. Patients with a persistent mass after chemotherapy measuring 2·5 cm or larger and positive on PET scan received additional radiotherapy with 30 Gy; the negative predictive value for tumour recurrence of PET at 12 months was an independent endpoint. This trial is registered with Current Controlled Trials, number ISRCTN32443041. FINDINGS: Of the 2182 patients enrolled in the study, 2126 patients were included in the intention-to-treat analysis set, 705 in the 8×B(esc) group, 711 in the 6×B(esc) group, and 710 in the 8×B(14) group. Freedom from treatment failure was sequentially non-inferior for the 6×B(esc) and 8×B(14) groups as compared with 8×B(esc). 5-year freedom from treatment failure rates were 84·4% (97·5% CI 81·0-87·7) for the 8×B(esc) group, 89·3% (86·5-92·1) for 6×B(esc) group, and 85·4% (82·1-88·7) for the 8×B(14) group (97·5% CI for difference between 6×B(esc) and 8×B(esc) was 0·5-9·3). Overall survival in the three groups was 91·9%, 95·3%, and 94·5% respectively, and was significantly better with 6×B(esc) than with 8×B(esc) (97·5% CI 0·2-6·5). The 8×B(esc) group showed a higher mortality (7·5%) than the 6×B(esc) (4·6%) and 8×B(14) (5·2%) groups, mainly due to differences in treatment-related events (2·1%, 0·8%, and 0·8%, respectively) and secondary malignancies (1·8%, 0·7%, and 1·1%, respectively). The negative predictive value for PET at 12 months was 94·1% (95% CI 92·1-96·1); and 225 (11%) of 2126 patients received additional radiotherapy. INTERPRETATION: Treatment with six cycles of BEACOPP(escalated) followed by PET-guided radiotherapy was more effective in terms of freedom from treatment failure and less toxic than eight cycles of the same chemotherapy regimen. Thus, six cycles of BEACOPP(escalated) should be the treatment of choice for advanced stage Hodgkin's lymphoma. PET done after chemotherapy can guide the need for additional radiotherapy in this setting. FUNDING: Deutsche Krebshilfe and the Swiss Federal Government.

µMLC-LINAC radiosurgery for intracranial meningiomas of complex shape.

BACKGROUND: We present the long-term results of a consecutive series of patients with meningiomas treated by LINAC-radiosurgery using the micro-multi-leaf collimator technique (µMLC). METHODS: Between May 2001 and July 2009, 78 patients (m: f = 024:54; median age, 56.8 years; range, 20.1-81 years) with 87 intracranial meningiomas (78 WHO I, seven WHO II, two WHO III) were treated with µMLC-LINAC radiosurgery at our institution, either as a primary or salvage treatment following one or more microsurgical procedures. Fifty-eight of 87 tumors (66.7%) were located in the skull base. The remaining 29 meningiomas (33.3%) were located in the convexity of the brain. The median tumor volume was 4.8 ml (range, 0.2-18.3 ml). The median tumor surface dose, maximal dose, and therapeutic isodose were 12 Gy, 16 Gy, and 75%, respectively. RESULTS: For retrospective evaluation, we included 70 patients (78 tumors) with a minimum radiological follow-up of 24 months. After a median follow-up of 79.7 months (range, 24.2-109.1 months), 24 patients (34.3%) improved in their clinical status (paresis of N. abducens 18/48, facial paresis 4/8, and hemiparesis 2/9), 41 patients remained stable (58.6%), three patients had treatment-related temporary complaints (4.3%); two patients developed vertigo, and one had a left-sided hemihypesthesia. All complaints recovered completely after steroid medication within 2 weeks. Two patients (2.8%) developed permanent trigeminal neuralgia. Follow-up MR images showed a partial remission in 21 tumors (26.9%) and a stable tumor size in 55 cases (70.5%). Two patients with high-grade meningiomas showed a tumor progression (one WHO II and one WHO III meningioma). At the end of follow-up (July 2010), the actuarial 5- and 9-year progression-free survival after radiosurgery were 98 and 96%, respectively. There was no treatment-related mortality. CONCLUSIONS: LINAC radiosurgery using a micro multi-leaf collimator for complex shaped intracranial meningiomas is effective yielding a high local tumor control, whereas the treatment-related morbidity remains low.

Evolution of radiation therapy within the German Hodgkin Study Group trials.

Since its beginning, more than 16,000 patients have been enrolled in the multicentric randomized trials of the German Hodgkin Study Group (GHSG) for adult patients. Within 6 study generations, the treatment of Hodgkin lymphoma has been developed stepwise by using the results of the completed protocols. Now the sixth generation is active. According to the role of radiotherapy, the study group successfully evaluated different dose-effect relationships and could also prove the efficacy of involved-field radiotherapy in early stages in combination with effective chemotherapy. Currently, a radiation dose of 20 Gy to the involved field after a mildly aggressive chemotherapy (2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD]) should be the standard for early-favorable stages according to the GHSG classification. In early-unfavorable or intermediate-risk stages, involved-field radiation therapy with 30 Gy is sufficient; the optimal chemotherapy has to be fixed. For the advanced stages, the question of radiotherapy is still unclear. Preliminary results of the GHSG and others show that additive radiotherapy after intensive chemotherapy might be useful for elective subgroups of patients. The extensive radiotherapy quality assurance program, performed by the GHSG and its radiotherapy reference center, has proven to be successful and necessary to ensure that, with reduced radiation doses and reduced radiation volumes, precise radiotherapy, as defined by the protocol, will be performed by the participating radiotherapy departments.

Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel : a phase II study.

PURPOSE: To report outcome and toxicity of concurrent radiochemotherapy with carboplatin and paclitaxel in advanced squamous cell carcinomas of the oropharynx and hypopharynx. PATIENTS AND METHODS: Advanced inoperable carcinomas of the oropharynx and hypopharynx were treated with either hyper-fractionated, accelerated radiotherapy (50.0 Gy/2.0 with concomitant boost to 69.2 Gy/1.6) or conventional fractionated radiotherapy (70.2-72 Gy/1.8) concurrent with paclitaxel 40 mg/m2 and carboplatin AUC 1 weekly for 6 weeks. Acute and long-term toxicity was measured according to WHO- and CTC-criteria. RESULTS: A total of 84 patients were included between 2000 and 2008. Median follow-up time of patients alive was 36 months. Conventionally fractionated radiotherapy was given to 16 patients, while 68 patients were treated with concomitant boost. Finally, 88.1% of patients received full dose paclitaxel. Acute mucositis ≥ grade 3 was present in 51.2% of patients, while 6% of patients experienced ≥ grade 3 leucopenia and thrombopenia. A supportive gastric feeding tube was implanted in 89.1% of patients. Overall survival after 2 years was 46.3%, progression-free survival after 2 years was 41.0%. There was no significant survival difference between the different radiotherapy protocols. CONCLUSION: Concomitant carboplatin and paclitaxel is feasible and effective in advanced carcinomas of the head and neck.

Stereotactic LINAC radiosurgery for incompletely resected or recurrent atypical and anaplastic meningiomas.

BACKGROUND: The optimal management of subtotally resected or recurrent malignant meningiomas remains controversial. We evaluated the efficacy of linear accelerator (LINAC) radiosurgery for atypical and anaplastic meningiomas after incomplete resection or treatment of recurrences. METHODS: Between August 1990 and December 2003, 16 patients with 28 meningiomas WHO II and III were treated by stereotactic LINAC radiosurgery at our institution. The median radiological follow-up was 60.3 months, respectively (range: 7.2-173.9 months). Fourteen tumors in nine patients were classified as WHO II and 14 tumors in seven patients as WHO III. The median surface dose was 14 Gy (range: 10-15 Gy) with a median tumor volume of 4.8 ml (range: 0.51-51.4 ml). RESULTS: Clinical condition improved in four patients, remained unchanged in nine and deteriorated in one. Tumor shrinkage was seen in eight of 28 meningiomas and a stable disease in 12. Eight of 28 meningiomas showed local tumor progression. The overall tumor control rate (TCR) was 84%, 70%, 70% after 3, 5, 10 years. According to grading the corresponding TCR after 3, 5, 10 years was 91%, 81%, 81% for grade II and 77%, 60%, 60% for grade III meningiomas. Overall progression-free survival (PFS) was 74%, 67%, 58% after 3, 5, 10 years. According to grading the PFS after 3, 5, 10 years was 88%, 75%, 75% for grade II meningiomas and 57%, 57%, 43% for grade III meningiomas. CONCLUSION: Our results show the efficacy and safety of LINAC radiosurgery for incompletely resected or recurrent malignant meningiomas with a relatively high local tumor control and low morbidity.

Radiotherapy of splenomegaly : a palliative treatment option for a benign phenomenon in malignant diseases.

PURPOSE: Since the 20(th) century, radiotherapy (RT) has been used for treatment of symptomatic splenomegaly (SM). SM occurs in association with hematologic disorders. The purpose of this analysis was to determine the indication, treatment concepts, and efficiency of RT. MATERIAL AND METHODS: Clinical features, treatment concepts, and outcome data during the past 20 years were analyzed. Endpoints were pain relief, symptomatic and hematological response, and treatment-related side effects. RESULTS: From 1989-2009, a total of 122 patients received 246 RT courses because of symptomatic SM. Overall 31 patients had chronic myelogenous leukemia (CML), 37 had chronic lymphocytic leukemia (CLL), 23 had osteomyelofibrosis (OMF), 17 had polycythemia vera (PV), 5 had acute myelogenous leukemia, 4 had idiopathic thrombocytopenic purpura (ITP), 3 had non-Hodgkin lymphoma (NHL), and 2 had multiple myeloma (MM). Patients were treated with (60)Co gamma rays or 5-15MV photons. The fraction size ranged from 10-200 cGy and the total dose per treatment course from 30-1600 cGy. Significant pain relief was achieved for 74.8% of the RT courses given for splenic pain. At least 50% regression was attained for 77% of the RT courses given for SM. 36 patients died within 2 months due to the terminal nature of their disease. Of the RT courses applied for cytopenia, 73.6% achieved a significant improvement of hematological parameters and reduction of transfusion need. Notable hematologic toxicities were reported < EORTC/RTOG II°. CONCLUSION: The present analysis documents the efficacy of RT. In addition, RT as a palliative treatment option for symptomatic SM should not be forgotten.

Neoadjuvant radiochemotherapy and surgery for advanced rectal cancer : prognostic significance of tumor regression.

PURPOSE: Preoperative radiochemotherapy is widely used in the treatment of locally advanced rectal cancer. The predictive value of response to neoadjuvant treatment remains uncertain. We retrospectively evaluated the impact of downstaging and tumor regression as prognostic factors and its influence on the ability to perform sphincter-sparing surgery. PATIENTS AND METHODS: A total of 72 consecutive patients with advanced rectal cancer were included in this retrospective analysis. All patients were treated with preoperative 5-fluorouracil-based chemotherapy and pelvic radiation with a total dose of 50.4 Gy followed by surgery 6 weeks later. RESULTS: A sphincter-preserving procedure could be performed on 42 patients, and in all 72 patients complete resection (R0) was achieved. A pathological complete response (ypT0, ypN0) was achieved in 8 (11%) patients. None of the patients showing a complete pathological response relapsed or died during the follow-up period. At a median follow-up of 28 months, 65 patients were alive, none of these patients had local recurrence and 15 patients had metastatic disease. Patients showing a complete pathological response had a significantly better 2-year disease-free survival compared to patients with ≥10% residual tumor cells (p = 0.024). Patients < 65 years showed a significantly better response rate, compared with those > 65 years of age (p = 0.036). Acute toxicity was moderate. CONCLUSION: Preoperative radiochemotherapy is an effective and safe treatment for patients with locally advanced rectal cancer. Pathological parameters after preoperative radiochemotherapy, including tumor regression grading, could be correlated with disease-free survival. The impact of tumor regression grading needs to be further validated in prospective clinical trials.

Combined-modality treatment in advanced oral squamous cell carcinoma: Primary surgery followed by adjuvant concomitant radiochemotherapy.

BACKGROUND: The efficacy of adjuvant radiochemotherapy (RCT) in patients with advanced stage head and neck carcinoma has been proven in prospective randomized trials. However, these trials focused on different head and neck sites. Specific analyses for treatment effects in squamous cell carcinoma of the oral cavity (OSCC) are missing. We evaluated our experiences with adjuvant concomitant RCT in advanced OSCC to compare the results with other treatment schemes using adjuvant RCT. PATIENTS AND METHODS: A total of 183 patients with OSCC of UICC stages II-IVb were reviewed retrospectively. All patients were treated with radical surgery followed by adjuvant, conventional fractionated concomitant RCT using carboplatin. Overall survival was plotted by Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analysis. RESULTS: Univariate analysis showed a significant impact of T, N, and UICC stage, histopathologic grading, surgical margins, extracaspular spread (ECS), and lymphangiosis carcinomatosa on overall survival (Table 3). Patients with stage IVa had a higher 5-year overall survival rate (42.8%) than patients with stage IVb (25.0%) (Figure 1). The differences were significant in multivariate analysis (p = 0.033) (Table 4). CONCLUSION: Adjuvant concomitant RCT is an effective treatment in patients with advanced stage OSCC. However, it remains unclear, which patients should be treated with adjuvant RCT. For patients with stage IVb, adjuvant RCT yields poor results. Prospective randomized trials are needed to confirm which patients should be treated with adjuvant RCT.

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) Hodgkin's 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 Hodgkin's 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 Hodgkin's 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.)

Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial.

PURPOSE: Combined-modality treatment consisting of four to six cycles of chemotherapy followed by involved-field radiotherapy (IFRT) is the standard of care for patients with early unfavorable Hodgkin's lymphoma (HL). It is unclear whether treatment results can be improved with more intensive chemotherapy and which radiation dose needs to be applied. PATIENTS AND METHODS: Patients age 16 to 75 years with newly diagnosed early unfavorable HL were randomly assigned in a 2 × 2 factorial design to one of the following treatment arms: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy of IFRT; four cycles of ABVD + 20 Gy of IFRT; four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP(baseline)) + 30 Gy of IFRT; or four cycles of BEACOPP(baseline) + 20 Gy of IFRT. RESULTS: With a total of 1,395 patients included, the freedom from treatment failure (FFTF) at 5 years was 85.0%, overall survival was 94.5%, and progression-free survival was 86.0%. BEACOPP(baseline) was more effective than ABVD when followed by 20 Gy of IFRT (5-year FFTF difference, 5.7%; 95% CI, 0.1% to 11.3%). However, there was no difference between BEACOPP(baseline) and ABVD when followed by 30 Gy of IFRT (5-year FFTF difference, 1.6%; 95% CI, -3.6% to 6.9%). Similar results were observed for the radiotherapy question; after four cycles of BEACOPP(baseline), 20 Gy was not inferior to 30 Gy (5-year FFTF difference, -0.8%; 95% CI, -5.8% to 4.2%), whereas inferiority of 20 Gy cannot be excluded after four cycles of ABVD (5-year FFTF difference, -4.7%; 95% CI, -10.3% to 0.8%). Treatment-related toxicity occurred more often in the arms with more intensive therapy. CONCLUSION: Moderate dose escalation using BEACOPP(baseline) did not significantly improve outcome in early unfavorable HL. Four cycles of ABVD should be followed by 30 Gy of IFRT.

Hodgkin's lymphoma in adolescents treated with adult protocols: a report from the German Hodgkin study group.

PURPOSE The standard of care for adolescent patients with Hodgkin's lymphoma (HL) is undefined, particularly the choice between pediatric and adult protocols. Thus, we compared risk factors and outcome of adolescents and young adults treated within study protocols of the German Hodgkin Study Group (GHSG). PATIENTS AND METHODS Three thousand seven hundred eighty-five patients treated within the GHSG studies HD4 to HD9 were analyzed; 557 patients were adolescents age 15 to 20 years, and 3,228 patients were young adults age 21 to 45 years. Results Large mediastinal mass and involvement of three or more lymph node areas were more frequent in adolescents (P < .001). The incidence of other risk factors did not differ significantly between age groups. With a median observation time of 81 months for freedom from treatment failure (FFTF) and 85 months for overall survival (OS), log-rank test showed no significant differences between age groups regarding FFTF (P = .305) and a superior OS (P = .008) for adolescents. Six-year estimates for FFTF and OS were 80% and 94%, respectively, for adolescents and 80% and 91%, respectively, for young adults. After adjustment for other predictive factors, Cox regression analysis revealed age as a significant predictor for OS (P = .004), with a higher mortality risk for young adults. Secondary malignancies were more common in young adults (P = .037). CONCLUSION Outcome of adolescent and young adult patients treated within GHSG study protocols is comparable. These data suggest that adult treatment protocols exhibit a safe and effective treatment option for adolescent patients with HL. However, longer follow-up, including assessment of late toxicity, is necessary for final conclusions.

Long-term outcome and prognostic factors in early-stage nodal low-grade non-hodgkin's lymphomas treated with radiation therapy.

PURPOSE: Retrospective analysis of therapy results in patients with stage I-II and limited stage III nodal low-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: The present retrospective study covers 65 patients treated between 1988 and 2006 at the Department of Radiation Oncology, University of Cologne, Germany. 50 patients were treated with radiotherapy alone (EF [extended field]: n = 35, IF/REG [involved field/regional field]: n = 9, TNI/TLI [total nodal/total lymphatic]: n = 6), 15 patients additionally received chemotherapy. Median age was 58 years. 58 patients presented with centroblastic-centrocytic or follicular lymphomas, seven patients had centrocytic lymphomas. Apart from overall and relapse-free survival, relapse patterns were examined and the impacts of patient characteristics and therapy modalities were analyzed. RESULTS: After a median follow-up of 9.1 years, overall 5-year and 10-year survival was 86% and 55%, relapse-free survival was 55% and 37%, respectively. Relapses occurred in 28 patients during the observation period. Overall survival was favorably influenced by low patient age (p = 0.037), centroblastic-centrocytic/follicular histology (p = 0.006), and early disease stage (p = 0.045). Favorable prognostic factors for relapse-free survival were low patient age (p = 0.035) and centroblastic-centrocytic/follicular histology (p = 0.001). CONCLUSION: Radiotherapy of early-stage low-grade NHL is a curative therapy option, particularly in younger patients and patients with follicular histology. Relapse analysis confirmed the benefits of total nodal or total lymphatic irradiation, although the small number of patients needs to be considered.

Randomized study of postoperative radiotherapy and simultaneous temozolomide without adjuvant chemotherapy for glioblastoma.

PURPOSE: To evaluate the efficacy of simultaneous postoperative temozolomide radiochemotherapy in glioblastoma patients. PATIENTS AND METHODS: From February 2002 to July 2004, n = 65 patients from 11 German centers with macroscopic complete tumor resection were randomized to receive either postoperative radiotherapy alone (RT, n = 35) or postoperative radiotherapy with simultaneous temozolomide (RT + TMZ, n = 30). Patients were stratified according to age (< or =/>50 years) and WHO performance score (0-1 vs. 2). RT consisted of 60 Gy in 30 fractions. In the RT + TMZ arm, oral TMZ was administered daily at a dose of 75 mg/m(2) including weekends (40-42 doses). Adjuvant treatment was not given, but in both arms, patients with recurrent tumors and in good condition (WHO 0-2) were scheduled for salvage chemotherapy with TMZ. RESULTS: The trial was stopped early due to the results of EORTC-study 26981-22981 that showed a survival benefit for the combination of concomitant and adjuvant TMZ compared to radiotherapy alone. In total, 62/65 patients were evaluable. Stratification variables were well balanced (< or = 50 years 26% vs. 20%, WHO 0-1 91% vs. 100%). Neither overall survival (median 17 vs. 15 months) nor progression-free survival (median 7 vs. 6 months) differed significantly between the two arms. In the RT (RT + TMZ) arm, 76% (62%) of the progressing patients received salvage chemotherapy with TMZ, 36% (50%) had a second resection. There was a time-constant trend for increased general quality of life (EORTC questionnaire QLQ C30) and brain-specific quality of life (EORTC questionnaire B20) in the combined arm. Lymphopenia G3-4 was more frequent (33 vs. 6%) in the RT + TMZ arm. CONCLUSION: After early closure of this trial, a benefit for progression-free survival for simultaneous TMZ radiochemotherapy alone could not be demonstrated. In both arms, salvage therapies were frequently used and probably had a major effect on overall survival.

Involved-node radiotherapy in early-stage Hodgkin's lymphoma. Definition and guidelines of the German Hodgkin Study Group (GHSG).

BACKGROUND AND PURPOSE: Radiotherapy of Hodgkin's Lymphoma has evolved from extended-field to involved-field (IF) radiotherapy reducing toxicity whilst maintaining high cure rates. Recent publications recommend further reduction in the radiation field to involved-node (IN) radiotherapy; however, this concept has never been tested in a randomized trial. The German Hodgkin Study Group aims to compare it with standard IF radiotherapy in their future HD17 trial. PATIENTS AND METHODS: ALL patients must be examined by the radiation oncologist before the start of chemotherapy. At that time, patients must have complete staging CT scans. For patients with IN radiotherapy, a radiation planning CT before and after chemotherapy with patients in the treatment position is recommended. Fusion techniques, allowing the overlapping of the pre- and postchemotherapy CT scans, should be used. Usage of PET-CT scans with patients in the treatment position is recommended, whenever possible. RESULTS: The clinical target volume encompasses the initial volume of the Lymph node(s) before chemotherapy and incorporates the initial Location and extent of the disease taking the displacement of the normal tissues into account. The margin of the planning target volume should be 2 cm in axial and 3 cm in craniocaudal direction. If necessary, it can be reduced to 1-1.5 cm. To minimize Lung and cardiac toxicity, the target definition in the mediastinum is different. CONCLUSION: The concept of IN radiotherapy has been proposed as a means to further improve the therapeutic ratio by reducing the risk of radiation-induced toxicity, including second malignancies. Field sizes wiLL further decrease compared to IF radiotherapy.

Quality control of involved field radiotherapy in patients with early-favorable (HD10) and early-unfavorable (HD11) Hodgkin's lymphoma: an analysis of the German Hodgkin Study Group.

PURPOSE: The German Hodgkin Study Group (GHSG) set up a radiotherapy (RT) reference center within the Department of Radiation Oncology at the University of Cologne to undertake quality assurance of the group's clinical studies. In the HD10 trial (early-favorable stages) and HD11 trial (early-unfavorable stages) all patients received involved field (IF)-RT (30 Gy vs. 20 Gy) within a combined-modality approach. For these patients a central prospective review of all diagnostic imaging was performed by expert radiation oncologists to control disease extension and to define IF treatment volume. METHODS AND MATERIALS: On the basis of simulation films, verification films, and radiotherapy case report form (CRF) an expert panel evaluated retrospectively the adequacy of irradiated IF treatment portals according to the RT prescription, applied radiation doses, treatment time, and technical parameters. RESULTS: Between 1999 and 2006 a total of 825 of 1370 randomized patients of the HD10 trial (60%) and 954 of 1422 patients of the HD11 trial (67%) were evaluated by the panel. Radiotherapy was rated as suboptimal in 47% of all reviewed cases. Although the participating RT centers received a precise RT prescription, most difficulties occurred in the adequate coverage of the IF (40%), followed by technical faults (12%). Deviations from the prescribed single daily dose (1.8-2 Gy), weekly dose, and total reference dose were rare (1%). CONCLUSIONS: As a consequence of these findings, radiation oncologists were trained on the definition of IF-RT at GHSG meetings and at the annual meetings of the German Society for Therapeutic Radiation Oncology. Possible correlations between RT quality and relapse rate will be investigated.

Neoadjuvant radiochemotherapy and radical resection for advanced squamous cell carcinoma of the oral cavity. Outcome of 134 patients.

BACKGROUND AND PURPOSE: Several multimodal strategies have been developed to treat patients with squamous cell carcinoma of the oral cavity. The advantages of preoperative radiochemotherapy are downstaging of the primary tumor, an increased resectability rate, and the elimination of micrometastases. After successful phase II trials, the following therapy regimen for resectable advanced oral carcinoma was applied. PATIENTS AND METHODS: 134 patients with resectable squamous cell carcinoma of the oral cavity stage II-IV received neoadjuvant radiochemotherapy consisting of 39.6 Gy in daily fractions of 1.8 Gy and concomitant carboplatin (70 mg/m(2) days 1-5). Radical resection and neck dissection were carried out afterwards. RESULTS: After a median follow-up of 73 months, 82 patients (61%) had died. 54 patients (40%) experienced locoregional relapses or distant metastases. The overall survival was 65% +/- 4% after 2 years and 45% +/- 4% after 5 years. Cox regression survival analysis identified tumor regression, extracapsular lymph node spread and resection state as prognostic factors. Side effects of grade 3-4 were rare. CONCLUSION: Neoadjuvant radiochemotherapy with subsequent radical surgery can be recommended as an effective and safe treatment for primary resectable advanced tumors of the oral cavity. Acute and long-term toxicities appear to be moderate.

Lymphocyte-predominant and classical Hodgkin's lymphoma: a comprehensive analysis from the German Hodgkin Study Group.

PURPOSE: Lymphocyte-predominant Hodgkin's lymphoma (LPHL) is rare and differs in histologic and clinical presentation from classical Hodgkin's lymphoma (cHL). To shed more light on the prognosis and outcome of LPHL, we reviewed all LPHL patients registered in the German Hodgkin Study Group (GHSG) database, comparing patient characteristics and treatment outcome with cHL patients. PATIENTS AND METHODS: We analyzed retrospectively 8,298 HL patients treated within the GHSG trials HD4 to HD12, of whom 394 had LPHL and 7,904 had cHL. RESULTS: Complete remission and unconfirmed complete remission after first-line treatment was achieved in 91.6% v 85.9% of patients in early favorable stages, 85.7% v 83.3% of patients in early unfavorable stages, and 76.8% v 77.8% of patients in advanced stages of LPHL compared with cHL, respectively. Tumor control (freedom from treatment failure [FFTF]) for LPHL and cHL patients at a median observation of 50 months was 88% and 82% (P = .0093) and overall survival (OS) was 96% and 92%, respectively (P = .0166). In LPHL patients, negative prognostic factors were advanced stage (P = .0092), Hb less than 10.5 g/dL (P = .0171), and lymphopenia (P = .010) for FFTF. Age >or= 45 years (P = .0125), advanced stage (P = .0153), and Hb less than 10.5 g/dL (P = .0014) were negative prognostic factors for OS. CONCLUSION: The better prognosis of LPHL as compared with cHL might allow different treatment strategies, particularly for early-stage LPHL patients.