Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European Group for Blood and Marrow Transplantation.

PURPOSE: The high rate of toxicity is the limitation of myeloblastive regimens before allogeneic transplantation. A reduced intensity regimen can allow engraftment of stem cells and subsequent transfer of immune cells for the induction of a graft-vs.-tumor reaction. METHODS AND MATERIALS: The data from 130 patients (80 males and 50 females) treated between 1998 and 2003 for various hematologic malignancies were analyzed. The median patient age was 50 years (range, 3-72 years). Allogeneic transplantation using peripheral blood or bone marrow, or both, was performed in 104 (82%), 22 (17%), and 4 (3%) patients, respectively, from HLA identical sibling donors (n = 93, 72%), matched unrelated donors (n = 23, 18%), mismatched related donors (4%), or mismatched unrelated donors (6%). Total body irradiation (TBI) at a dose of 2 Gy delivered in one fraction was given to 101 patients (78%), and a total dose of 4-6 Gy was given in 29 (22%) patients. The median dose rate was 14.3 cGy/min (range, 6-16.4). RESULTS: After a median follow-up period of 20 months (range, 1-62 months), engraftment was obtained in 122 patients (94%). Acute graft-vs.-host disease of Grade 2 or worse was observed in 37% of patients. Multivariate analysis showed three favorable independent factors for event-free survival: HLA identical sibling donor (p < 0.0001; relative risk [RR], 0.15), complete remission (p < 0.0001; RR, 3.08), and female donor to male patient (p = 0.006; RR 2.43). For relapse, the two favorable prognostic factors were complete remission (p < 0.0001, RR 0.11) and HLA identical sibling donor (p = 0.0007; RR 3.59). CONCLUSIONS: In this multicenter study, we confirmed high rates of engraftment and chimerism after the reduced intensity regimen. Our results are comparable to those previously reported. Radiation parameters seem to have no impact on outcome. However, the lack of a statistically significant difference in terms of dose rate may have been due, in part, to the small population size in the subgroup analysis.

Common strategy for adult and pediatric medulloblastoma: a multicenter series of 253 adults.

PURPOSE: To assess prognostic factors for adults with medulloblastoma in a multicenter, retrospective study. METHODS AND MATERIALS: Data were collected by file review or mail inquiry for 253 adults treated between 1975 to 2004. Radiologists or surgeons assessed disease characteristics, such as volume and extension. Patients were classified as having either high- or standard-risk disease. Prognostic factors were analyzed. RESULTS: Median patient age was 29 years. Median follow-up was 7 years. Radiotherapy was delivered in 246 patients and radiochemotherapy in 142. Seventy-four patients relapsed. Respective 5- and 10-year overall survival rates were 72% and 55%. Univariate analysis showed that survival significantly correlated with metastasis, postsurgical performance status, brainstem involvement, involvement of the floor of the fourth ventricle (V4), and radiation dose to the spine and to the posterior cerebral fossa (PCF). By multivariate analysis, brainstem, V4 involvement, and dose to the PCF were negative prognostic factors. In the standard-risk subgroup there was no overall survival difference between patients treated with axial doses of >or=34 Gy and patients treated with craniospinal doses <34 Gy plus chemotherapy. CONCLUSION: We report the largest series of medulloblastoma in adults. Prognostic factors were similar to those observed in children. Results suggest that patients with standard-risk disease could be treated with radiochemotherapy, reducing doses to the craniospinal area, maintaining at least 50 Gy to the PCF. The role of chemotherapy for this group is still unclear. A randomized study should be performed to confirm these results, but because frequency is very low, such a study would be difficult.

Radiotherapy for solitary extramedullary plasmacytoma in the head-and-neck region: A dose greater than 45 Gy to the target volume improves the local control.

PURPOSE: Our aim was to determine the dose to the clinical target volume (CTV) required for solitary extramedullary plasmacytoma (EMP) in the head and neck (HN). METHODS AND MATERIALS: Seventeen patients (15 Stage I and 2 Stage II) were treated for HN EMP at our institution between 1979 and 2003. The mean International Commission on Radiation Units (ICRU) dose prescribed to the CTV was 52.6 Gy (range, 40-65 Gy) over 24 fractions (range: 20-30). The Stage II patients received neck irradiation doses of 40 and 60 Gy. A mean dose of 36.4 Gy was used for 5 Stage I patients who received elective neck irradiation. Dose administrated to the CTV was evaluated from dosimetric data or from planning films when dosimetric data were not available. Two groups of patients were distinguished: CTV covered with a dose greater than 40 Gy and CTV covered with a dose greater than 45 Gy. RESULTS: The 5-year local control was 72.8%. It was 100% for patients who received dose to the CTV > or = [DOSAGE ERROR CORRECTED] 45 Gy vs. 50% for dose to the CTV <45 Gy (p = 0.034). The prognostic factor for 5-year disease-specific survival (81.6%) was local control (p = 0.058). The prognostic factors for disease-free survival (64.1%) were monoclonal immunoglobulin secretion (p = 0.008) and a CTV dose > or = 45 Gy (p = 0.056) CONCLUSIONS: Local control of EMP in the HN seems to be improved when the dose to the CTV is > or = [DOSAGE ERROR CORRECTED] 45 Gy. A minimum dose of 45 Gy should be recommended to the CTV.

Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk medulloblastoma without chemotherapy: results of the French M-SFOP 98 protocol.

PURPOSE: Between December 1998 and October 2001, patients <19 years old were treated for standard-risk medulloblastoma according to the Medulloblastome-Société Française d'Oncologie Pédiatrique 1998 (M-SFOP 98) protocol. Patients received hyperfractionated radiotherapy (36 Gy in 36 fractions) to the craniospinal axis, a boost with conformal therapy restricted to the tumor bed (to a total dose of 68 Gy in 68 fractions), and no chemotherapy. Records of craniospinal irradiation were reviewed before treatment start. RESULTS: A total of 48 patients were considered assessable. With a median follow-up of 45.7 months, the overall survival and progression-free survival rate at 3 years was 89% and 81%, respectively. Fourteen major deviations were detected and eight were corrected. No relapses occurred in the frontal region and none occurred in the posterior fossa outside the boost volume. Nine patients were available for volume calculation without reduction of the volume irradiated. We observed a reduction in the subtentorial volume irradiated to >60 Gy, but a slight increase in the volume irradiated to 40 Gy. No decrease in intelligence was observed in the 22 children tested during the first 2 years. CONCLUSION: This hyperfractionated radiotherapy protocol with a reduced boost volume and without chemotherapy was not associated with early relapses in children. Moreover, intellectual function seemed to be preserved. These results are promising.

Influence of dose point and inverse optimization on interstitial cervical and oropharyngeal carcinoma brachytherapy.

BACKGROUND AND PURPOSE: Evaluation of the use of optimization methods in interstitial cervical and oropharyngeal brachytherapy; evaluation of the conformal index (COIN) and the natural dose ratio (NDR) to quantify the implant quality. MATERIAL AND METHODS: CT-based dose distributions were obtained for seven implants according to the Paris system. CT-based implants were used to assess the dose point and inverse optimization methods. To compare the results of these planning methods, the coverage index (CI), normal tissue irradiation (NTI), and the protection of organs at risk (OARs) were evaluated using cumulative dose volume histograms (CDVH). RESULTS: In regular cervical implants, a CI of 94 and 96%; a NTI of 35 and 28% resulted for non-optimized and optimized implants, respectively. In irregular cervical implants, a CI of 88, 96, and 90%; a NTI of 44, 37, and 44% resulted for non-optimized, dose point optimized, and inverse optimized implants, respectively. Compared to the non-optimized implants; both optimization methods resulted in better protection for the bladder wall. As for the protection of the rectal wall, only the inverse optimization gave a better result. In oropharyngeal implants, a better CI resulted after dose point optimization. Irradiation of the contralateral parotid were improved after both optimization methods. The maximum change in COIN that could have been achieved by optimization was 3%, as CI and NTI increased similarly. For the same value of COIN, an underdosage of PTV was avoided by the optimization methods as NDR increased from 0.86 to 1.01. CONCLUSION: CT-based optimized implant allows conformation of the dose distribution to the PTV while sparing normal tissue and organs at risk. COIN and NDR should be used together to evaluate both doses to normal tissue and organs at risk, and an under- or overdose inside the PTV.

Late effects of post-high-dose-rate brachytherapy for oropharyngeal carcinoma: are they severer than post-low-dose-rate?

BACKGROUND: . Late effects by high-dose-rate (HDR) brachytherapy have been believed severer than low-dose-rate (LDR) provided tumor control was constant. Local control of oropharyngeal carcinoma with HDR at Osaka Medical Center was comparable to LDR series from Centre Alexis Vautrin (82%, 79.5%, respectively). To assess the feasibility of HDR brachytherapy, the late effects were compared. PATIENTS AND METHODS: . The data of 29 HDR and 24 LDR patients (median follow-up of 27 and 29.5 months, respectively; p = 0.89) were collected. The HDR schedule was 21 Gy/3.5 fractions/2 days following 46 Gy/23 fractions external beam, while 25 Gy/3 days following 50 Gy/25 fractions external beam was for LDR. Late changes were evaluated using RTOG/EORTC late morbidity scoring scheme. For subclinical late changes, mucosa chapter of Dische score was modified for brachytherapy. Scores were discussed through photos and were agreed on by authors. Late sequelae were estimated, by reviewing charts, concerning frequency, severity, and duration of mucosal damages (erosion and ulcer). RESULTS: . Late changes were of no difference (p = 0.12 for EORTC/RTOG, and p = 0.45, 0.47, 1.00, 0.12, 0.16, 0.95, 0.27, 0.21 for erythema, ulceration, edema, thinning, pallor, telangiectasia, mobility impairment of tongue/faucial pillars, respectively, of the modified Dische score). Late sequelae showed no differences (p = 0.90, 0.12, 0.40 for frequency, severity, duration, respectively, of mucosal damages). CONCLUSION: . The late effects by HDR were not severer than by LDR. HDR oropharyngeal brachytherapy is as safe as LDR.

[Standards, Options and Recommendations 2000: non metastatic endometrial cancer]. / Standards, Options et Recommendations 2000: cancer de l'endomètre, stades non métastatiques (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, and specialists from French Public Universities, General Hospitals and Private Clinics, and some specialists learned societies. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The SORs are developed using a methodology based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the management of patients with carcinoma of the endometrium according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 63 independent reviewers. RESULTS: The main recommendations for the management of carcinoma of the endometrium are: 1) The diagnosis of carcinoma of the endometrium is based on biopsy and histological examination. However, as first intention, the first elements for diagnosis can be obtain from a hysterography, or particularly, a endovaginal ultrasound examination. Ultrasound allows locoregional metastases to be detected, the CT scan allows the lymph node involvement to be assessed and magnetic resonance imaging allows the myometrium invasion to be evaluated. 2) For the majority of patients, surgery is the initial treatment, both for localised and advanced-stage carcinomas. The excised sample can be used for pathological analysis and tumour staging, using the FIGO (Fédération internationale de gynécologie obstétrique) classification. Surgery for patients with stage I and II carcinomas involves total extrafascial hysterectomy with bilateral salpingo-oophorectomy., In patients with stage III and IV carcinomas radical surgery should be performed, when possible. If this is not possible, then surgery should be as complete as possible and be associated with a complementary treatment. In patients with the most advanced carcinomas, tumour reduction by surgery should be performed. 3) Complementary treatment includes external-beam radiotherapy and brachytherapy. The decision concerning the extent and type of irradiation should be taken taking into consideration the stage and the prognostic factors present. For patients with stage I and II carcinoma, complementary treatment with brachytherapy can be performed, if the myometrium invasion is not deep, or if the carcinoma is grade 2 or 3. Patients with stage III carcinomas can be treated with pelvic or abdominal-pelvic complementary irradiation. In patients that cannot undergo surgery, exclusive radiotherapy can be performed. 4) In the absence of any symptoms, surveillance should include a general clinical and gynaecological examination. All patients with symptoms should undergo an additional work-up.

Postoperative brachytherapy alone and combined postoperative radiotherapy and brachytherapy boost for squamous cell carcinoma of the oral cavity, with positive or close margins.

BACKGROUND: Postoperative radiotherapy is necessary for squamous cell carcinoma (SCC) of the oral cavity with positive or close margins. The aim of the study is to define the indications of postoperative brachytherapy (BRT). METHODS: From 1979 to 1993, 82 patients with positive or close margins had postoperative BRT (58 T1-2, 24 T3-4, 45 mobile tongue, 37 floor of mouth). Forty-six patients had combined radiotherapy (RT) with a mean dose of 48 Gy, and BRT boost with a mean dose of 24 Gy. Thirty-six patients had BRT alone with a mean dose of 60 Gy. BRT was performed with interstitial low dose rate Iridium 192. RESULTS: Overall survival (OS), cause-specific survival (CSS), and local control (LC) at 5 years were, respectively, for T1-2/N0N- with BRT, 75%, 85%, and 88%,and with RT-BRT 70%, 92%, and 92%; for T1-2/N+ with RT-BRT, 44%, 67%, and 78%; for T3-4/N- with RT-BRT, 42%, 90%, and 80%; and for T3-4/N+ with RT-BRT, 22%, 43%, and 57%. Prognostic factors for OS, CSS, and LC were N+ (p