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Early-stage Hodgkin's disease: long-term results with radiotherapy alone or combined radiotherapy and chemotherapy.

BACKGROUND: Controversy still exists over the optimal management of early-stage Hodgkin's disease (HD); presentation features may have a different prognostic impact according to initial therapy, and long-term toxicity must be fully evaluated. PATIENTS AND METHODS: This study included 164 patients with stage IA-IIA HD treated with radiotherapy (RT) alone or combined radio- and chemotherapy (CT) according to presenting features and their attendant prognostic significance. The RT group included 88 patients with favorable prognostic features; the combined modality group included 76 patients with one or more unfavorable features. In the RT group, 85% of patients received extended-mantle or STNI; in the combined modality group, RT consisted of mantle- (49%), extended mantle- (37%), and involved-field irradiation (14%); CT consisted of 6 cycles of MOPP before 1984; 3 cycles of ABVD were substituted for MOPP thereafter. RESULTS: Complete remission was obtained in 94% and 99% of patients of the RT and combined modality groups, respectively. The 10-year actuarial relapse-free survival (RFS) in the RT group was 62% and was influenced by stage (p = 0.04) and histology (p = 0.01); in the combined modality group, RFS was 88% and was influenced by the presence of bulky disease. Overall survival and tumor mortality between the therapy groups were comparable. RT-related toxicity consisted of mediastinal fibrosis (8 cases), myelitis (3), hypothyroidism (2); other long-term events included 2 cases of acute leukemia in the combined MOPP and RT group. Altogether, 8 of 20 patients who died were in their first complete remission. CONCLUSIONS: In stage IA-IIA HD, the combined modality therapy reduced the risk of relapse compared to radiation alone; long-term toxicity of RT was not negligible and relapses could occur late.

Adolescent↗

Hypofractionated stereotactic radiotherapy using intensity-modulated radiotherapy in patients with one or two brain metastases.

PURPOSE: A small fraction of patients with 1-2 brain metastases will not be suitable candidates to either surgical resection or stereotactic radiosurgery (SRS) due to either their location or their size. The objective of this study was to determine the local control, survival, patterns of relapse and the incidence of brain injury following a course of hypofractionated stereotactic radiotherapy while avoiding upfront whole brain radiation therapy (WBRT) in this subgroup of patients. METHODS: A Gill-Thomas removable head frame system was used for immobilization. Brain LAB software with dynamic multileaf collimator hardware was used to design and deliver an intensity-modulated radiation therapy treatment plan. A dose of 600 cGy was prescribed to the 100% isodose line that would encompass the lesion with a 3-mm margin. A total dose of 3,000 cGy was delivered in 5 fractions using 2 fractions per week. The patients were followed with neurological examination and serial MRI images done every 3 months following the procedure. RESULTS: Twenty patients have been treated using this fractionation schedule since April 2004. The 1-year local control at the site of original disease is 70%. The complete response, partial response and stable disease at the last follow-up were 15, 30 and 45%, respectively. Two patients had local recurrence at the site of original disease, while 5 had evidence of leptomeningeal disease. Two additional patients developed new brain metastases, resulting in a 1-year brain relapse-free survival of 36% following this approach. The median overall survival was 8.5 months. Three patients (15%) developed steroid dependency lasting 3 months or longer following the procedure. Four patients (20%) needed WBRT as salvage following this approach. CONCLUSIONS: The preliminary results of hypofractionated SRS are comparable to both surgery and SRS data for solitary brain metastases in terms of local control and overall survival with acceptable morbidity in this cohort of unfavorable patients.

Adult↗

Radiotherapy alone and radiotherapy followed by radical mastectomy in T2 breast cancer.

Ninety-four patients with T2 NO, N1a, N1b, MO were treated with primary radiotherapy (RT) because of old age or poor general conditions. In 32 patients (34%), younger in age and in better general conditions, Halsted radical mastectomy could be performed 5-8 months from starting RT; surgery was not done at random, but decided case by case on the basis of a good response to RT and an improvement of general status. Relapse was documented in 42 patients. Relapse rate was 50% in the group treated with RT alone (high incidence of breast recurrences) and 33% in the group operated on after RT. Distant metastases had the same incidence in the 2 groups, with a median free interval of 14 months. Overall disease-free survival rates at 5 to 10 years were 46% and 35%, respectively; these results are not particularly different from the data of historical series of T2 breast cancer treated with surgery alone. The patients operated on after RT had a significantly better survival, but the results were clearly influenced by the selection of patients. For the future, a safe policy could be a conservative combined treatment consisting of tumorectomy followed by curative RT; adjuvant medical therapy could be scheduled for high-risk patients (N1b).

Adult↗

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.

Adult↗

Importance of radiotherapy in the outcome of patients with primary CNS lymphoma: an analysis of the CHOD/BVAM regimen followed by two different radiotherapy treatments.

PURPOSE: To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen. PATIENTS AND METHODS: Patients received one cycle of CHOD and two of BVAM. In the first trial, all 31 patients received 45-Gy whole-brain RT (CHOD/BVAM I). In the second, with 26 patients, RT dose was reduced to 30.6 Gy if there was a complete response (CR) after chemotherapy (CHOD/BVAM II). RESULTS: Age, performance status, and chemotherapy received were similar in both protocols. CR rate at the end of all treatment was 68% for CHOD/BVAM I and 77% and for CHOD/BVAM II. Treatment modality was the only predictor of relapse, with 3-year relapse risks of 29% and 70% for CHOD/BVAM I and II, respectively. This was specifically important in the 25 patients less than 60 years old (3-year relapse risk, 25% v 83%; P =.01). The 5-year overall survival (OS) was 36%. Age (< 60 v > or = 60 years) was the only predictor for OS in the multivariate analysis (relative risk, 2.1; 95% confidence interval, 1.4 to 2.8). RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment (3-year OS, 92% v 60% for patients receiving 45 or 30.6 Gy, respectively; P =.04). CONCLUSION: Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR resulted in an increased risk of relapse and lower OS.

Actuarial Analysis↗

Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402.

PURPOSE: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are treated with surgery and radiotherapy (RT) at diagnosis, but they also respond to procarbazine, lomustine, and vincristine (PCV), raising the possibility that early chemotherapy will improve survival. Furthermore, better outcomes in AO have been associated with 1p and 19q allelic loss. PATIENTS AND METHODS: Patients with AO and AOA were randomly assigned to PCV chemotherapy followed by RT versus postoperative RT alone. The primary end point was overall survival. The status of 1p and 19q alleles was assessed by fluorescence in situ hybridization. RESULTS: Two hundred eighty-nine eligible patients were randomly assigned to either PCV plus RT (n = 147) or RT alone (n = 142). At progression, 80% of patients randomly assigned to RT had chemotherapy. With 3-year follow-up on most patients, the median survival times were similar (4.9 years after PCV plus RT v 4.7 years after RT alone; hazard ratio [HR] = 0.90; 95% CI, 0.66 to 1.24; P = .26). Progression-free survival time favored PCV plus RT (2.6 years v 1.7 years for RT alone; HR = 0.69; 95% CI, 0.52 to 0.91; P = .004), but 65% of patients experienced grade 3 or 4 toxicity, and one patient died. Patients with tumors lacking 1p and 19q (46%) compared with tumors not lacking 1p and 19q had longer median survival times (> 7 v 2.8 years, respectively; P < or = .001); longer progression-free survival was most apparent in this subset. CONCLUSION: For patients with AO and AOA, PCV plus RT does not prolong survival. Longer progression-free survival after PCV plus RT is associated with significant toxicity. Tumors lacking 1p and 19q alleles are less aggressive or more responsive or both.

Adult↗

Effectiveness of RF capacitive hyperthermia combined with radiotherapy for stages III and IV oro-hypopharyngeal cancers: a non-randomized comparison between thermoradiotherapy and radiotherapy.

Seventy-two patients with Stages III and IV (TNM, UICC, 1987) squamous-cell carcinoma of the oropharynx and hypopharynx (oro-hypopharyngeal cancer) were treated with external irradiation, or irradiation plus 13.56 MHz radiofrequency (RF) capacitive hyperthermia from 1989 to 1995. This study compared initial response, histological effect and 5-year survival rate of thermoradiotherapy (TRT) group with those of radiotherapy alone (RT) group. In the TRT group, 15 patients were treated definitively, and 18 patients preoperatively. In the RT group, 15 patients were treated definitively, and 24 patients preoperatively. With definitive irradiation, the complete response rate of the primary lesions was 73% in the TRT group and 27% in the RT group (p = 0.009) and the complete response rate of the metastatic lymph nodes was 80% in the TRT group and 27% in the RT group (p = 0.005). With preoperative irradiation, the pathological CR (No residual cancerous cells) rate of the primary lesions was 56% in the TRT group and 8% in the RT group (p = 0.01), and the pathological CR rate of the lymph nodes was 72% in the TRT group and 21% in the RT group (p = 0.001). The 5-year survival rates with definitive irradiation were 47.6% in the TRT group and 18.7% in the RT group (p = 0.025). Thus TRT was more effective than RT for advanced oro-hypopharyngeal cancer.

Aged↗

Acute and delayed effects of radiotherapy in patients with oesophageal squamous cell carcinoma treated with chemotherapy, surgery and pre- and postoperative radiotherapy.

Among 73 patients with oesophageal squamous cell carcinoma treated with chemotherapy (cisplatin + 5-fluorouracil), surgery and pre- and postoperative radiotherapy, the 1-year survival rate was 68% and the 5-year rate 26%. The treatment was well tolerated, though there were 11 cases of pericardial or pleural effusion, in all of which the effusion was benign and could be successfully treated with pleural aspiration and/or pleurodesis, pericardiocentesis, or in one case pericardectomy.

Antineoplastic Combined Chemotherapy Protocols↗

A randomized trial of radiotherapy versus radiotherapy plus CCNU for incompletely resected low-grade gliomas: a Southwest Oncology Group study.

Sixty adult patients with incompletely excised low-grade gliomas were randomly assigned to receive radiotherapy (55 Gy over a total of 6 1/2 to 7 weeks) either alone or with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; 100 mg/sq m every 6 weeks). Pathological review showed that six patients were ineligible for the study. Evaluation of patient age, extent of surgery, tumor grade, and performance status showed no significant differences between the treatment arms. The response rate, as judged by the disappearance or reduction in size of the tumor on computerized tomography scans, was 79% for radiation therapy alone versus 54% for irradiation plus CCNU. The median survival time was 4.45 years for all patients, with no significant difference between treatment arms (p = 0.7). For the group as a whole, patient age and performance status were the most important prognostic parameters. The majority of patients receiving chemotherapy experienced moderate hematological toxicity. This study demonstrates that CCNU chemotherapy does not improve the results of radiation therapy in the treatment of incompletely excised low-grade gliomas.

Adult↗

[Non-small-cell bronchial carcinoma with pathological N2 involvement: adjuvant radiotherapy versus adjuvant chemo-radiotherapy].

Fifty-eight patients, 28 of them included in a German multicenter study, were treated either with radiotherapy (5 x 2 Gy/50 Gy) or combined radio-chemotherapy (cisplatin 75 mg/m2 d1 in cases with pneumonectomy etoposide 120 mg/m2 d1-3) and Ifosfamid 1.5 mg/m2 d1-4, 3 cycles) following surgery in pN2-NSCLC. Metastatic disease or local failure was seen in 24 patients (43%), in the majority with distant metastasis (n = 21), in 4 patients combined local and distant failure. Time to progression (TTP) was 27 to 1172 days, median 244 days. Median survival of the whole group was 873 days (= 29 months), the 3-year survival 49%. Comparing the two groups there was an advantage (not significant) in favor of the combined treated group with a median survival of 1449 days versus 765 days (p = 0.22).

Antineoplastic Combined Chemotherapy Protocols↗

Retrospective comparison of clinical outcome between radiotherapy alone and surgery plus postoperative radiotherapy in the treatment of stages IB-IIB cervical squamous cell carcinoma.

PURPOSE: To determine retrospectively whether radical surgery plus postoperative radiotherapy (RT) is superior to definitive RT from the standpoint of disease control and adverse events in the treatment of stages IB-IIA and stage IIB cervical squamous cell carcinoma. MATERIALS AND METHODS: The study included 143 patients treated by definitive RT (stages IB-IIA, n = 15; stage IIB, n = 27) or postoperative RT (stages IB-IIA, n = 67; stage IIB, n = 34). Cause-specific survival (CSS) and recurrence-free rate (RFR) were estimated. Late adverse events (proctitis, cystitis, lymphedema, and ileus) were graded, and the incidences were estimated. RESULTS: Overall, 5-year CSS and RFR did not differ significantly between patients treated with definitive RT (80.4% and 69.7%, respectively) and those treated with postoperative RT (80.6% and 79.1%, respectively). Rates according to clinical stage also did not differ significantly between the two types of treatment. Grades 1-3 adverse events occurred. Grades 2-3 lymphedema and Grades 2-3 ileus, but not Grades 2-3 cystitis, occurred significantly often with postoperative RT. CONCLUSION: Despite no difference in survival or patterns of recurrence, adverse events were significantly more frequent with postoperative RT than with definitive RT for both stages IB-IIA and stage IIB disease.

Adult↗

Ten-year results of randomized trial comparing radiotherapy and concomitant bleomycin to radiotherapy alone in epidermoid carcinomas of the oropharynx: experience of the European Organization for Research and Treatment of Cancer.

This trial of treatment for head and neck carcinoma was initiated in 1973 by the European Organization for Research and Treatment of Cancer. Its purpose was to investigate the value of single-agent chemotherapy with bleomycin (BLM) given during the course of a conventional treatment by external radiotherapy (RT) compared to treatment by external RT alone. In this randomized study, we compared treatment results in 2 groups of patients with squamous cell carcinoma of the oropharynx (T2, T3, and T4; International Union Against Cancer classification). One group of 92 patients was treated by RT at the prescribed dose of 70 Gy. The other group of 107 patients received radiation according to the same protocol and simultaneously received im injection of BLM at a dose of 15 mg twice a week, 2 hours prior to the session of RT, for a total dose of 150 mg in 5 weeks. The occurrence of local toxic effects (i.e., mucositis and epidermatitis) was significantly greater in the RT-BLM group (RT-BLM, 72%, vs. RT, 21%). Primary tumor response 6 weeks after completion of RT was the same in both arms of the study (RT, 68%, vs. RT-BLM, 67%). The 6-year survival rate was 24% (RT-BLM) versus 22% (RT). Long-term analysis (10 yr) is given.

Bleomycin↗

[The cost of radiotherapy. Evaluation of the real cost of treatments performed in a radiotherapy service of a center for fight against cancer].

The authors present a retrospective analysis dealing with the cost of therapeutic procedures achieved in the department of radiotherapy of the Centre Claudius-Regaud. This analysis was performed according to the actual cost of the different components of each treatment including the human costs. For this last purpose, serial countings of time spent by each category of employees were performed and then translated into financial terms. Results show a large discrepancy between the costs of therapeutic procedures. These differences are mainly related to the purpose of therapeutic plan, dealing with the most expensive procedures dealing with the developmental treatments. This study provides a tool that can be used by medical and/or administrative managers of radiation oncology departments when changes or innovations in therapeutic procedures. This cost accounting analysis is compared to the French administrative procedures used to pay the health care services and to determine the level of hospital resources.

Brachytherapy↗

[Comparison of concomitant radiotherapy and chemotherapy with radiotherapy alone in advanced cancers of the head and neck: results of a randomized trial].

From April 1987 to October 1992, 67 patients with inoperable squamous cell carcinoma of the head and neck region were included in a randomized trial. All patients had induction chemotherapy with cisplatin (100 mg/m2, D1) and fluorouracil (1 g/m2, from D1 to D5) every three weeks for a total of three cycles. Patients were randomized to concurrent external radiation therapy (70 Gy/39 fractions/8 weeks) and chemotherapy with cisplatin (50 mg/m2 in short infusion, D1, D15, D29, D43) and fluorouracil (5 mg/kg, intra-muscular, every Monday, Wednesday and Friday) (experimental group) versus radiotherapy alone with the same modalities (control group). The followup for living patients was 14 to 60 months with a median of 42 months. Analysis of preliminary results has shown that: 1) early and late side effects are similar in both groups; 2) after completion of treatment, the percentage of patients in complete remission was 71% (20/28) in the experimental group and 43% (12/28) in the control group; this difference was statistically significant among non responders to induction chemotherapy (1/15 versus 13/20, P = 0.001), but non significant among responders (11/13 versus 7/8) and 3) there were no differences between both randomized groups in term of 3-year overall survival and of 3-year loco-regional control. Results are discussed taking into account a review of literature.

Antineoplastic Combined Chemotherapy Protocols↗

Intraindividual comparison of conventional three-dimensional radiotherapy and intensity modulated radiotherapy in the therapy of locally advanced non-small cell lung cancer a planning study.

BACKGROUND: Local failure is the one of the most frequent cause of tumor related death in locally advanced non-small cell lung cancer (LAD-NSCLC). Dose escalation has the promise of increased loco-regional tumor control but is limited by the tolerances of critical organs. PATIENTS AND METHODS: To evaluate the potential of IMRT in comparison to conventional three-dimensional conformal planning (3DCRT) dose constraints were defined: Maximum dose (D(max)) to spinal cord < 48 Gy, mean lung dose </= 24 Gy, D(max) esophagus > 70 Gy in not more than 5 cm of the total length. For ten patients two plans were compared: (1) 3DCRT with 5 weekly fractions (SD) of 2 Gy to a total dose (TD) of 50 Gy to the planning target volume of second order (PTV2). If the tolerance of the critical organs was not exceeded, patients get a boost plan with a higher TD to the PTV1. (2) IMRT: concomitant boost with 5 weekly SD of 2 Gy (PTV1) and 1.5 Gy to a partial (p)PTV (pPTV=PTV2 profile of a line PTV1) to a TD of 51 Gy to the pPTV and 68 Gy to the PTV1. If possible, patients get a boost plan to the PTV1 with 5 weekly SD of 2 Gy to the highest possibly TD. RESULTS: Using 3DCRT, 3/10 patients could not be treated with TD > 50 Gy, but 9/10 patients get higher TD by IMRT. TD to the PTV1 could be escalated by 16% on average. The use of non-coplanar fields in IMRT lead to a reduction of the irradiated lung volume. There is a strong correlation between physical and biological mean lung doses. CONCLUSION: IMRT gives the possibility of further dose escalation without an increasing mean lung dose especially in patients with large tumors.

Adult↗

Combined chemotherapy and radiotherapy versus surgery and postoperative radiotherapy for advanced hypopharyngeal cancer.

BACKGROUND: Although the standard therapy for locally advanced hypopharyngeal cancer remains surgery and postoperative radiotherapy (RT), alternative treatment approaches include induction chemotherapy and RT. The purpose of this retrospective study was to compare the long-term outcome of these treatments performed in a single institution. METHODS: Twenty-six patients with advanced, resectable, squamous cell carcinoma of the hypopharynx were treated with induction chemotherapy and definitive RT (group I), reserving laryngectomy for salvage. The induction phase of therapy consisted of 2-3 cycles of cisplatin-based chemotherapy followed by conventional fractionated RT to doses of 66-70 Gy. The outcomes of this group of patients were compared with the outcomes of 30 patients with hypopharyngeal cancer who were treated at our institution with surgery and postoperative RT (group II). The median follow-up times of the surviving patients in groups I and II were 5 and 9 years, respectively. RESULTS: The local recurrence-free survival at 5 years from the completion of therapy for group I was 50%, compared with 69% for group II (p = .41). Among patients with T3-T4 primary tumors, the 5-year local control rates were 58% and 59% for groups I and II, respectively (p = .78). The likelihood of larynx preservation, free of local disease at 5 years for group I, was 52%. The 5-year neck recurrence-free survival for groups I and II were 47% and 69%, respectively (p = .66). Among patients with N2-N3 stage disease, the 5-year incidence of neck failure for groups I and II were 73% and 68%, respectively (p = .74). The 5-year distant metastases-free survival for groups I and II were 67% and 57%, respectively (p = .19). The 5-year disease-free survival rates for groups I and II were 30% and 42%, respectively (p = .9). The 5-year overall survival rates for groups I and II were 15% and 22%, respectively (p = .65). CONCLUSIONS: Nonsurgical therapy for advanced stage hypopharyngeal cancer provides survivorship comparable with that achieved with standard approaches of surgery and postoperative RT. However, despite the therapy, the outcome is poor. Future studies will need to explore new treatment strategies in an effort to improve upon the outcome for this group of patients.

Adult↗