Salvage Radiation Therapy for Intracranial Germinoma Recurring After Primary Chemotherapy

Systemic chemotherapy has been increasingly used in the primary treatment of intracranial germinoma. However, the recurrence rate seems to be very high after treatment with chemotherapy alone. We used radiation to treat 5 patients harboring intracranial germinoma that recurred following primary chemotherapy. They had received systemic chemotherapy (4 with cisplatin plus etoposide and 1 with adriamycin, vincristine, cyclophosphamide, prednisolone, and cisplatin) 7–24 months before referral. All patients were treated with conventional radiotherapy directed to the primary tumor site or the craniospinal axis with a dose to the primary site ranging from 39.6 to 47.0 Gy (mean, 42.6 Gy). Response to radiation of all the recurrent tumors was good and all tumors disappeared on diagnostic imaging below the dose of 24 Gy. All patients are alive without further recurrence at 61–129 months after salvage radiotherapy. Germinomas recurring after primary chemotherapy do not seem to have acquired cross resistance to radiotherapy. They can usually be cured by standard radiation therapy with 40–47 Gy.     

Local therapy in localized Ewing tumors: results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials

PURPOSE: The impact of different local therapy approaches on local control, event-free survival, and secondary malignancies in the CESS 81, CESS 86, and EICESS 92 trials was investigated. METHODS AND MATERIALS: The data of 1058 patients with localized Ewing tumors were analyzed. Wherever feasible, a surgical local therapy approach was used. In patients with a poor histologic response or with intralesional and marginal resections, this was to be followed by radiotherapy (RT). In EICESS 92, preoperative RT was introduced for patients with expected close resection margins. Definitive RT was used in cases in which surgical resection seemed impossible. In CESS 81, vincristine, adriamycin, cyclophosphamide, and actinomycin D was used. In CESS 86, vincristine, adriamycin, ifosfamide, and actinomycin D was introduced for patients with central tumors or primaries >100 cm(3). In CESS 92, etoposide, vincristine, adriamycin, ifosfamide, and actinomycin D was randomized against vincristine, adriamycin, ifosfamide, and actinomycin D in patients with primaries >100 cm(3). RESULTS: The rate of local failure was 7.5% after surgery with or without postoperative RT, and was 5.3% after preoperative and 26.3% after definitive RT (p = 0.001). Event-free survival was reduced after definitive RT (p = 0.0001). Irradiated patients represented a negatively selected population with unfavorable tumor sites. Definitive RT showed comparable local control to that of postoperative RT after intralesional resections. Patients with postoperative RT had improved local control after intralesional resections and in tumors with wide resection and poor histologic response compared with patients receiving surgery alone. Patients with marginal resections with or without postoperative radiotherapy showed comparable local control, yet the number of patients with good histologic response was higher in the latter treatment group (72.2% vs. 38.5%). CONCLUSION: Patients with resectable tumors after initial chemotherapy had a low local failure rate. With preoperative RT, local control was comparable. RT is indicated to avoid intralesional resections. After intralesional or marginal resections and after a poor histologic response and wide resection, postoperative RT may improve local control.     

Patterns of treatment failure in pediatric and young adult patients with Hodgkin's disease: local disease control with combined-modality therapy.

PURPOSE: Refinement in managing pediatric Hodgkin's disease (HD) requires understanding of factors associated with local treatment failure. This study defines the cumulative incidence (CI) of local failure (LF) and prognostic factors for pediatric patients treated for HD with combined-modality therapy (CMT). PATIENTS AND METHODS: We enrolled 195 patients onto two prospective studies at St Jude Children's Research Hospital between 1990 and 2000. Patients received CMT with chemotherapy (vinblastine, doxorubicin, methotrexate, and prednisone [VAMP]; vinblastine, etoposide, prednisone, and doxorubicin; or VAMP/cyclophosphamide, vincristine, and procarbazine) and involved-field radiation therapy delivered to initial site(s) of disease on the basis of early response. Sites of disease involvement, treatment, and sites of failure were confirmed from the patients' medical record, imaging, and radiotherapy treatment records. We estimated the overall survival, event-free survival, and CI of LF. RESULTS: With a median follow-up of 7.6 years, the CI of LF was 10.9% and 11.6% at 5 and 10 years, respectively. Twenty-seven (14%) of 195 patients experienced recurrence of HD, and 22 (81%) of those experienced LF. Bulky mediastinal disease greater than one third transthoracic diameter predicted a higher incidence of LF, but did not predict failure in the mediastinum. Male sex, low initial hemoglobin, and bulky mediastinal disease were prognostic indicators of LF. Attenuation of radiation dose to 15 Gy based on response provides excellent infield control. CONCLUSION: CMT provides excellent local disease control in children and young adults with HD. LF remains a primary site of disease recurrence, with male sex, low initial hemoglobin, and bulky mediastinal disease predicting for LF.     

Second malignancies after treatment for Ewing’s sarcoma: a report of the CESS-studies

Purpose: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing’s sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing’s Sarcoma Studies CESS 81 and CESS 86.Materials and Methods: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing’s sarcoma trials CESS 81 (recruitment period 1981–1985) and CESS 86 (1986–1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete surgery (n = 162), surgery plus postoperative radiotherapy with 36–46Gy (n = 274), or definitive radiotherapy with 46–60Gy (n = 212). The median follow-up at the time of this analysis was 5.1 years, the maximum follow-up 16.5 years.Results: The overall survival of all patients including metastatic patients was 55% after 5 years, 48% after 10 years, and 37% after 15 years. Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (n = 1), and three were sarcomas. The interval between diagnosis of Ewing’s sarcoma and the diagnosis of the SM was 17–78 months for the four AMLs, 96 months for the MDS and 82–136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 years. Out of five patients with AML/MDS, three died of rapid AML-progression, and two are living with disease. Local therapy (surgery vs. surgery plus postoperative irradiation vs. definitive radiotherapy) had no impact on the frequency of AML/MDS, but local therapy did influence the risk of secondary sarcomas. All three patients with secondary sarcomas had received radiotherapy; however, all three sarcomas were salvaged by subsequent treatment and are in clincal remission with a follow-up of 1 month, 4.3 years, and 7.5 years after the diagnosis of the secondary sarcoma. Thus far, SM contributed to less than 1% (3/328) of all deaths in the CESS-studies.Conclusions: The risk of leukemia after treatment for Ewing’s sarcoma is probably in the range of 2%. The risk of solid tumors also seems to be low within the first 10 years after treatment and remains in the range of 5% after 15 years. In the CESS-studies, less than 1% of all deaths within the first 10 years after diagnosis were caused by SM. Effective salvage therapy for secondary sarcomas is feasible.     

The optimal dose of radiation in Hodgkin's disease: an analysis of clinical and treatment factors affecting in-field disease control.

PURPOSE: The purpose of this study is to analyze the effect of radiation dose, as well as other clinical and therapeutic factors, on in-field disease control. PATIENTS AND MATERIALS: The study population comprised 232 patients with Stage I and II Hodgkin's disease (HD) treated with curative intent at the University of Florida with radiotherapy (RT) alone (169 patients) or chemotherapy and radiotherapy (CMT) (63 patients). Sites of involvement and radiation doses were prospectively recorded and correlated with sites of disease recurrence. RESULTS: Freedom from relapse and absolute survival rates at 10 years were as follows: 76% and 77%, entire group; 76% and 80%, RT group; 79% and 70%, CMT group; 85% and 78%, Stage I; and 71% and 77%, Stage II. Treatment failure occurred in 50 patients (22%) including in-field failure in 22 patients (9%). In-field failure was rare in electively treated sites. Multivariate analysis of clinical factors (tumor size, number of sites involved, B-symptoms, gender, histology, age, and site of involvement) and treatment factors (use of chemotherapy, number of cycles of chemotherapy, radiation dose, radiation treatment volume, and radiation treatment time) showed only tumor size (p = 0.0001) to be significantly correlated with in-field disease control. In RT patients, the in-field failure rate according to tumor size was as follows: 0% for < or = 3 cm; 4% for > 3 cm and < or = 6 cm; 23% for > 6 cm and < or = 9 cm; and 36% for > 9 cm. In CMT patients, the in-field failure rate was as follows: 0% for < or = 3 cm; 0% for > 3 and < or = 6 cm; 5% for > 6 cm and < or = 9 cm; and 26% for > 9 cm. In-field recurrence was not a predominant pattern of failure in RT patients with small tumors (< or = 6 cm); thus, the difference in in-field control in tumors < or = 6 cm between doses < or = 35 Gy (6%) and doses > or = 36 Gy (0%) was not statistically significant. In larger tumors (> 6 cm), in-field recurrence was a predominant pattern of failure; the in-field failure rate in RT patients with tumors > 6 cm of 30% for doses < or = 35 Gy was not significantly different from 25% for doses > 35 Gy. In moderately bulky tumors (> 6 cm and < or = 9 cm), the addition of chemotherapy did appear to increase in-field disease control; the in-field failure rate was 23% with RT and 5% with CMT (p = 0.07). CONCLUSION: Our data do not demonstrate statistically significant evidence of increasing tumor control in HD with doses > 30 Gy. The data do show that increasing tumor size is associated with increased rates of in-field failure, and the addition of chemotherapy may improve in-field disease control in tumors > 6 cm. In-field recurrence in large tumors remains a predominant pattern of failure, however, and the role of radiation doses higher than 30-35 Gy in this high-risk subset warrants further study.     

A multidisciplinary study investigating radiotherapy in Ewing’s sarcoma: end results of POG #8346

Purpose: To determine if involved field radiation (IF) is equivalent to standard whole bone radiation (SF) in local tumor control; to establish patterns of failure following treatment; and to determine response, event-free survival (EFS), and overall survival rates from multidisciplinary therapy in Ewing’s sarcoma.Methods and Materials: Between 1983 and 1988, 184 children with Ewing’s sarcoma were enrolled onto Pediatric Oncology Group 8346 (POG 8346). A total of 178 (97%) met eligibility criteria; 6 had pathology other than Ewing’s sarcoma. Induction chemotherapy of cyclophosphamide/doxorubicin (adriamycin )(C/A) x 12 weeks was followed by local treatment either surgery or radiation therapy and C/A, dactinomycin, and vincristine for 50 weeks. Resection was advised for patients with small primary tumors if accomplished without functional loss. Forty patients were randomized to receive SF, whole bone radiation to 39.6 Gy plus a 16.2 Gy boost (total 55.8 Gy) or IF to 55.8 Gy, and the remainder were assigned to IF radiation.Results: Of 178 eligible patients, 141 (79%) had localized disease and 37 (21%) had metastases at presentation. Their 5-year EFS was 51% (SE 5%) and 23% (SE 7%) respectively. The response rate to induction chemotherapy was 88% (28% complete, 60% partial), but after radiotherapy the response rate increased to 98%. Thirty-seven of the localized patients underwent resection, of whom 16 (43%) required postoperative radiotherapy; the 5-year EFS of these surgical patients was 80% (SE 7%). The remaining 104 localized patients were eligible for randomization or assignment to receive radiotherapy; the 5-year EFS of these patients was 41% (SE 5%), with no significant difference in EFS between those randomized to SF vs. IF. Site of primary tumor correlated with 5-year EFS: distal extremity 65% (SE 8%), central 63% (SE 10%), proximal extremity 46% (SE 8%), and pelvic–sacral 24% (SE 10%) (p = 0.004). Initial tumor size did not correlate significantly with EFS. Patterns of failure among the 141 localized patients revealed 23% of patients experienced a local failure, while 40% had a systemic failure. The 5-year local control rate for the surgical patients +/- postoperative radiotherapy was 88% (SE 6%), while for the patients undergoing radiotherapy alone it was 65% (SE 7%). There was no difference in local control between those randomized to SF vs. IF. The 5-year local control rate for the patients with pelvic–sacral tumors was 44% (SE 15%), significantly worse than the local control rates for those with central tumors 82% (SE 8%), distal extremity 80% (SE 8%), or proximal extremity 69% (SE 9%) (p = 0.023). However, quality of radiotherapy correlated with outcome. Patients who had appropriate radiotherapy had a 5-year local control of 80% (SE 7%), while those with minor deviations had 5-year local control of 48% (SE 14%), and those with major deviations had a local control of only 16% (SE 15%) (p = 0.005). The local failure was within an irradiated volume in 62% of patients, outside the irradiated volume in 24% of cases, while the precise location could not be determined in the remaining 14%.Conclusions: As most failures in Ewing’s sarcoma are systemic, improved EFS requires more effective systemic chemotherapy. Adequate IF radiotherapy requires treatment to appropriate volumes as defined by MRI imaging and full radiation doses. Pretreatment review of radiologic images with a musculoskeletal radiologist to determine appropriate tumor volumes, as well as use of conformal radiotherapy techniques are important for improved outcome.     

Ewing's sarcoma: local tumor control and patterns of failure following limited-volume radiation therapy

Sixty children with localized osseous Ewing's sarcoma were treated between 1978 and 1988 with induction chemotherapy (cyclophosphamide, adriamycin), irradiation and/or surgery, and 10 months of maintenance chemotherapy (cyclophosphamide, adriamycin, dactinomycin, vincristine). Following induction chemotherapy, 43 patients received primary radiation therapy to limited radiation volumes defined by post-chemotherapy residual soft tissue tumor extension and initial osseous tumor extent. Irradiation was defined as low dose at 30-36 Gy (median 35 Gy) for 31 cases with objective response to induction chemotherapy and high dose at 50-60 Gy (median 50.4 Gy) for 12 patients with poor response to induction chemotherapy or with tumors greater than or equal to 8 cm. Overall event-free survival at 5 years is 59% and local tumor control is 68%. Initial failures have been local (12), simultaneous local and distant failures (7), and distant (6). In the surgical resection group, 14 patients had complete resection without radiation therapy, and 3 patients had microscopic residual plus 35-41 Gy; 100% local control has been maintained. In 43 patients with primary radiation therapy group, local tumor control is 58% (p = .004). Despite limited radiation volume, 18/19 local failures occurred centrally within the bone, well within the radiation volume. Imaging response to induction chemotherapy predicted local tumor control in the radiation therapy group: 62% with complete response/partial response versus 17% with no response/progressive disease (p less than 0.01). Local tumor control related strongly to primary tumor size in the radiation therapy group; among 31 cases receiving 35 Gy, local tumor control is 90% for lesions less than 8 cm versus 52% for tumors greater than or equal to 8 cm (p = .054). The central pattern of local failure in this experience suggests the effectiveness of limited radiation volume. The overall local tumor control rate following the tested dose level of 35 Gy appears to be inadequate, although results in selected cases with tumors less than 8 cm in greatest tumor dimension indicate potential efficacy in a yet limited experience.     

Integration of chemotherapy and radiation therapy for small cell carcinoma of the lung

Two chemotherapy trials using cyclophosphamide, doxorubicin hydrochloride and high-dose vincristine sulfate with or without methotrexate have induced a 93% incidence of complete remission in limited disease presentation of small cell bronchogenic carcinoma of the lung and 39% incidence in extensive disease. The first trial without consolidation radiotherapy had a local failure rate of 65%, which dropped to 17% with consolidation radiotherapy to the primary and mediastinum. Prophylactic whole brain radiotherapy prevented local recurrence in 98% of evaluable patients. One carcinomatous meningitis and 5 intraspinal recurrences were noted among the 38 patients in the CAV-M trial. We conclude that high-dose vincristine sulfate is associated with an improved incidence of complete remission; that prophylactic whole brain radiotherapy has been highly successful; that prevention of intraspinal recurrence will necessitate the use of craniospinal axis radiation therapy and consolidation radiation therapy improves local control of primary and mediastinum.     

Management and results of localized Ewing's sarcoma.

Seventy-six patients with localized Ewing's sarcoma who received primary treatment at M.D. Anderson Hospital from 1948 through December 1975 were reviewed. Patients have been divided into four groups according to the different treatment regimens they received: Group I, moderate dose radiotherapy alone; Group II, high dose radiotherapy alone; Group III, radiotherapy plus vincristine and cytoxan; and Group IV, radiotherapy plus vincristine, Adriamycin, cytoxan and actinomycin. The problem of local recurrence appears to be solved with combined chemotherapy and radiation therapy with only one of 36 patients having a recurrence at the primary site in Groups III and IV. Multimodal therapy is the preferred treatment to obtain control of the primary lesion by radiation therapy while preserving good function. However, the major cause of failure remains distant metastases, 19 of 36 (53%) in Groups III and IV. In addition, 4 of 10 patients who have survived over 5 years have developed osteogenic sarcoma.     

Dose-response relationship of nasopharyngeal carcinoma above conventional tumoricidal level: a study by the Hong Kong nasopharyngeal carcinoma study group (HKNPCSG).

BACKGROUND AND PURPOSE: To define the dose-response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66 Gy when the basic radiotherapy (RT) course was given by the 2D Ho's technique. PATIENTS AND METHODS: Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n = 2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho's technique. The primary endpoint was local control. The prognostic significance of dose-escalation ('boost') after 66 Gy, T-stage, N-stage, use of chemotherapy, sex and age (< or =40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed. RESULTS: On multivariate analysis, T-stage (P < 0.01; hazard ratio [HR], 1.58) and optimal boost (P = 0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P = 0.01; HR, 0.33); use of a boost (P < 0.01; HR, 0.60) and age (P = 0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20 Gy-boost gave a lower local failure rate than a 10 Gy-boost. There was no apparent excess mortality attributed to RT complications. CONCLUSIONS: Within the context of a multi-center retrospective study, dose-escalation above 66 Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho's technique without additional chemotherapy. 'Boosting' in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity.     

Failure pattern and factors predictive of local failure in rhabdomyosarcoma: a report of group III patients on the third Intergroup Rhabdomyosarcoma Study.

PURPOSE: To analyze patterns of failure and factors predictive of local treatment failure in children enrolled on the third Intergroup Rhabdomyosarcoma Study who had either biopsy only or subtotal resection of their primary tumor, had no distant metastases, and received radiation therapy for local control. PATIENTS AND METHODS: Treatment failure was categorized as local, regional nodal, or distant metastatic. The 5-year cumulative risk of failure was estimated for each category and factors predictive of local failure risk were determined using the Cox model and binary recursive partitioning. RESULTS: The estimated 5-year cumulative incidence rates by failure category were: total local (with or without concurrent regional or distant failure), 19%; total regional nodal, 2%; total distant, 11%; and death from toxicity or unknown recurrence type, 4%. Lymph node involvement at diagnosis was the single factor most predictive of increased total local failure risk (5-year cumulative incidence 32%) compared with children with negative nodes or unknown node status (16%). No significant effect on local failure risk was observed by total radiotherapy dose over the prescribed range of 41.4 Gy to 50.4 Gy. For all patients (N = 405), the estimated 5-year failure-free survival and overall survival were, respectively, 70% and 78%. CONCLUSION: Local failure after radiotherapy for group III rhabdomyosarcoma patients is the predominant type of relapse. Involved lymph nodes at diagnosis predict a higher risk of local and distant treatment failure compared with patients whose lymph nodes are negative.     

Radiation-induced osteosarcoma arising 20 years after the treatment of Ewing's sarcoma

We report the case of a 17 years old female with a Ewing's sarcoma of the left femur treated with limb sparing surgery followed by local radiotherapy of 45 Gy and adjuvant chemotherapy with vincristine, doxorubicine, cyclophosphamide, actinomycin D. The patient received neoadjuvant chemotherapy for osteosarcoma and a left femur resection with endoprosthesis replacement. The patient is alive and free of disease 4 years after the treatment of this second malignant neoplasm (SMN). This case shows that radioinduced SMN can occurr with relatively low doses of RT (<50 Gy) and that it may occur very late.     

食管癌同期放化疗后局部失败相关因素分析

背景和目的:目前同期放化疗是不能手术食管癌的标准治疗方法,局部未控和复发仍是治疗失败的主要原因。本文主要总结我科收治的食管癌同期放化疗后局部未控和复发情况,分析影响局部未控和复发的相关因素。方法:对132例食管癌患者行同期放化疗。第一周期化疗与放射治疗同时开始,第二周期化疗在放疗剂量达40Gy时给予。以二项分类logistic回归分析影响局部未控和复发的因素。结果:至随访截止时间,全组患者射野内未控和复发54例,射野内未控和复发并淋巴结或其他器官转移20例,射野外复发5例。logistic回归分析显示与局部未控和复发相关的因素为近期疗效和放疗剂量。放疗后病灶完全缓解和部分缓解者,局部未控和复发率分别为44.9%和79.6%(P<0.001),平均复发时间分别为12.9个月和6.1个月(P=0.002)。放疗剂量为50～60Gy、60.1～69.9Gy、≥70Gy时,局部未控和复发率分别为69%、61%、52%(P=0.027),平均局部失败时间分别为5.3个月、9.1个月、10.3个月(P=0.038)。结论:影响局部未控和复发的因素为近期疗效和放疗剂量。     

The role of local radiation therapy for mediastinal disease in adults with T-cell lymphoblastic lymphoma

BACKGROUND: Mediastinal recurrence remains the most common cause of failure in patients with mediastinal T-cell lymphoblastic lymphoma (LBL). The role of mediastinal radiation therapy in improving local disease control and overall prognosis is not well-known with modern intensive chemotherapy. The objective of this study was to investigate the role of mediastinal radiation therapy in patients who achieve a complete response (CR) to chemotherapy. METHODS: The authors reviewed 47 patients with mediastinal T-cell LBL with or without bone marrow (BM) involvement who presented between 1980 and 1998. The median patient age was 25 years, and 33 patients (70%) were males. BM involvement was present in 16 patients (34%), 5 patients (11%) were in leukemic phase, lymph node involvement in was present 23 patients (49%), hepatosplenomegaly was present in 4 patients (9%), and pleural effusions were present in 22 patients (45%). The initial chemotherapy regimens were fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) in 23 patients; cyclophosphamide, vincristine, doxorubicin, and dexamethasone in 9 patients; vincristine, doxorubicin, and dexamethasone in 4 patients; cyclophosphamide, doxorubicin, vincristine, and prednisone in 4 patients; and other in 7 patients. Forty-three patients achieved a CR to chemotherapy and were the subject of this analysis. Nineteen of those patients received adjuvant mediastinal radiation therapy at a dose ranging from 26 grays (Gy) to 39 Gy. RESULTS: There was no difference in patient characteristics between the 19 patients who were treated with mediastinal radiation therapy and the 24 patients who did not receive mediastinal radiation therapy. The median follow-up for all 43 patients was 43 months. The 5-year overall survival (OS) rate was 66%, and the freedom from progression (FFP) rate was 64%. None of 19 patients who received radiation therapy experienced a mediastinal recurrence compared with 8 of 24 patients who did not receive radiation therapy and experienced a mediastinal recurrence. Patients who were treated with mediastinal radiation therapy had a significantly better mediastinal FFP rate (P = 0.01), but the differences in overall FFP and OS rates were not significant (P = 0.14 and P = 0.25, respectively). The effectiveness of the hyper-CVAD regimen seemed to underscore the role of mediastinal radiation therapy; only 2 patients experienced a recurrence among 16 patients who received mediastinal radiation therapy, both outside the mediastinum. This compared with two patients who experienced a recurrence among six patients who did not receive mediastinal radiation therapy, both in the mediastinum. CONCLUSIONS: Local radiation therapy significantly decreased the risk of mediastinal recurrence in adult patients with mediastinal T-cell lymphoblastic lymphoma. The benefit of adjuvant radiation therapy was particularly evident in patients treated with more intensive chemotherapy regimens.     

Cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy and radiotherapy for stage I intermediate or high grade non-Hodgkin's lymphomas: results of a strategy that adapts radiotherapy dose to the response after chemotherapy.

BACKGROUND: A limited number cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy followed by involved field radiotherapy is the treatment of choice for Ann Arbor stage I intermediate or high grade non-Hodgkin's lymphomas (NHL). The optimal radiotherapy dose in this combined modality setting, resulting in maximal disease control with minimal toxicity is unknown. In this retrospective single-center study we evaluated the results of a combined modality treatment strategy that adapts the radiotherapy dose to the response after chemotherapy, and focus on the influence of radiotherapy dose on local control and survival. PATIENTS AND METHODS: One hundred and forty patients with NHL Ann Arbor stages I/IE of intermediate or high grade malignancy received four cycles of CHOP chemotherapy followed by involved field radiotherapy (IF-RT). The radiotherapy dose for patients in complete response (CR) after CHOP was either 26 or 40 Gy. Patients in partial response (PR) after CHOP always received 40 Gy. The influence of the radiotherapy dose on treatment outcome was evaluated for patients in CR at the end of treatment (n=128). RESULTS: CR rates after chemotherapy and after radiotherapy were 67 and 91%, respectively. Seventy-four of the patients in CR after CHOP received 26 Gy, 20 patients in CR after CHOP 40 Gy. All patients in PR after CHOP (n=34) received 40 Gy. The localization of relapse (within or outside the radiation field) did not differ between patients receiving 26 or 40 Gy. Overall survival (OS) at 5 years for patients in CR after CHOP who received 26 and 40 Gy and for patients in PR after CHOP but CR after 40 Gy IF-RT was 76, 100 and 75%, respectively, (P=0.16), disease free survival (DFS) at 5 years 69, 90 and 75%, respectively, (P=0.52). CONCLUSIONS: No statistically significant differences in patterns of relapse or survival were found between patients receiving 26 or 40 Gy IF-RT, however the number of events in all subgroups was small.     

Effect of increasing radiation doses on local and distant failures in patients with localized prostate cancer

PURPOSE: To study the effect of radiation dose on local failure (LF) and distant metastasis (DM) in prostate cancer patients treated with external beam radiotherapy. METHODS AND MATERIALS: The study sample consisted of 919 Stage T1-T3N0M0 patients treated with radiotherapy alone. Three separate dose groups were analyzed: <72 Gy (n = 552, median dose, 68.4 Gy), > or =72 but <82 Gy (n = 215, median dose, 78 Gy), and > or =82 Gy (n = 152, median dose, 83 Gy). The median follow-up period for all patients and those receiving <72 Gy, > or =72 but <82 Gy, and > or =82 Gy was 97, 112, 94, and 65 months, respectively. RESULTS: For all patients, the LF rate at 10 and 15 years was 6% and 13%, respectively. The 7-year LF rate stratified by dose group (<72 Gy, > or =72 but <82 Gy, and > or =82 Gy) was 6%, 2%, and 2%, respectively (p = 0.012). For all patients, the DM rate at 10 and 15 years was 10% and 17%, respectively. The 7-year DM rate stratified by dose group (<72 Gy, > or =72 but <82 Gy, and > or =82 Gy) was 9%, 6%, and 1%, respectively (p = 0.008). Multivariate analysis revealed T stage (p < 0.001), pretreatment prostate-specific antigen level (p = 0.001), Gleason score (p < 0.001), and dose (p = 0.018) to be independent predictors of DM. For all 919 patients, multivariate analysis revealed only Gleason score (p = 0.009) and dose (p = 0.004) to be independent predictors of LF. CONCLUSION: Although the effect of increasing radiation doses has been documented mostly for biochemical failure rates, the results of our study have shown a clear association between greater radiation doses and lower LF and DM rates.     

Recurrent intracranial germinoma outside the initial radiation field: a single-institution study

Between 1975 and 2005, we treated 52 newly diagnosed germinoma patients. Until 1991, patients with pure germinomas or germinomas with syncytiotrophoblastic giant cells (STGCs) received whole-brain radiotherapy only. Of the 52 patients, 30 were treated with a reduced radiation volume and combined chemotherapy; seven of these received local irradiation with 24 Gy, two received whole-brain (30 Gy) plus local irradiation (20 Gy), 16 received extended local irradiation delivered to the whole ventricles (30 Gy) plus local (20 Gy) irradiation, and five received extended local irradiation (24 Gy). Of the 30 patients treated with a reduced radiation volume and combined chemotherapy, four experienced tumor recurrence; three patients had been treated with 24 Gy of local radiotherapy and one had received extended local (30 Gy) plus local (20 Gy) irradiation in addition to chemotherapy. In these patients, the delivered radiotherapy was inadequate and the origin of the recurrent tumors was outside the radiation field. None of the patients who had received at least 24 Gy of whole ventricle radiotherapy combined with chemotherapy experienced tumor recurrence. In combination with chemotherapy, the delivery of irradiation covering the ventricles effectively reduced the incidence of tumor recurrence in patients with germinomas or germinomas with STGCs.     

Prognostic factors affecting the outcome of nasopharyngeal carcinoma

BACKGROUND: The aim of the study is to evaluate patients with nasopharyngeal carcinoma treated with multisegmental intensity-modulated radiotherapy with or without chemotherapy and analyze patient, tumor and treatment characteristics, determining outcome. METHODS: From June 1999 through to April 2003, we treated in our institution 83 patients with nasopharyngeal carcinoma, 70 males and 13 females, their ages ranging from 25 to 85 years (median, 48 years). Nineteen patients had T1 tumors, 35 had T2 tumors, six had T3 tumors and 23 had T4 tumors. Sixty-four patients had cervical lymph node metastasis. Twenty patients were treated with radiation therapy alone and 63 patients with concurrent chemoradiotherapy. Cumulative radiation dose to primary tumor ranged from 70.2 to 77.4 Gy (median, 75.6 Gy). Follow-up ranged from 3 to 41.53 months (median, 17 months). RESULTS: Local complete response was achieved in 81 patients (97.5%). Local failure was observed in two patients, nodal failure in one patient and systemic failure in 14 patients. Overall survival, disease-free survival and disease-specific survival were 83, 84 and 93%, respectively, at 1 year, 82, 74 and 88%, respectively, at 2 years and 82, 61 and 88%, respectively, at 3 years. In univariate analysis, T stage of disease was a significant predictor of disease-free survival favoring those with early-stage (T1 + T2) disease (P = 0.040). Cumulative radiation dose to primary tumor was a significant predictor of disease-specific survival favoring those with >75.6 Gy (P = 0.010). Stage of disease (P = 0.007), N-classification (P = 0.046) and cumulative dose to primary tumor (P = 0.046) were significant prognostic factors for overall survival. CONCLUSIONS: High locoregional control for nasopharyngeal carcinoma was achieved with multisegmental intensity-modulated radiotherapy. Distant metastases are still the main impact on survival. More effective chemotherapy regimens and other systemic agents are needed to decrease the rate of distant metastasis.     

Influence of radiotherapy treatment concept on the outcome of patients with localized ependymomas

PURPOSE: To assess the outcome of 57 patients with localized ependymomas treated with radiotherapy (RT). METHODS AND MATERIALS: Fifty-seven patients with localized ependymomas were treated with RT. Histology was myxopapillary ependymoma (n = 4), ependymoma (n = 23), and anaplastic ependymoma (n = 30). In 16 patients, irradiation of the craniospinal axis (CSI) was performed with a median dose of 20 Gy. Forty-one patients were treated with local RT, with a local dose of 45 Gy to the posterior fossa, including a boost to the tumor bed of 9 Gy. In 19 patients, the tumor bed was irradiated with a median dose of 54 Gy. RESULTS: Overall survival after primary diagnosis was 83% and 71% at 3 and 5 years. Five-year overall survival was 80% in low-grade and 79% in high-grade tumors. Survival from RT was 79% at 3 and 64% at 5 years. We could not show a significant difference in overall survival between CSI and local RT only. Freedom of local failure was 67% at 5 years in patients treated with CSI and 60% at 5 years after local RT. A rate of 83% for distant failure-free survival could be observed in the CSI group as opposed to 93% in the group receiving local RT only. CONCLUSION: Local RT in patients with localized tumors is equieffective to CSI. The radiation oncologist must keep in mind that patients with localized ependymomas benefit from local doses > or =45 Gy.     

Local control of operable breast cancer after radiotherapy alone

221 patients with operable breast carcinoma stage Tis, T1, T2, T3, N0N1 were treated with radiotherapy alone without tumorectomy. The mean follow-up time was 15.5 years (range 5–22). The annual risk for local recurrence was 3% during the first 5 years and 1% during the following 10 years, resulting in an actuarial local control rate of 75.4% after 15 years. The risk for local recurrence was assessed in multivariate analysis and was significantly related to the size of the tumour measured on mammography (P = 0.0002), the radiation dose administered (P = 0.0018), the length of the split-course intervals being longer than 75 days (P = 0.001) and age (P = 0.019). Dose was related to response over a wide range as a function of tumour volume. All 18 patients with minimal tumour load (T0 and Paget's disease) treated with doses above 55 Gy in 6 weeks achieved local control. 5-year local control rates ranged from 40 to 100% for T1 carcinomas treated with 45–110 Gy, and from 0 to 95.3% for T2 carcinomas at the same dose. For T3 carcinomas local control varied between 50 and 83% at 60–110 Gy. The risk for local failure increased by 8% per cm tumour diameter. With exclusive radiotherapy, the doses needed to provide local control rates similar to those obtained after tumorectomy and irradiation are 10 Gy higher for T1 (95% 5 year control) and 35 Gy higher for T2 (90% 5 year control).