Search

A second intensification is an option at first relapse in multiple myeloma (MM) after more than 36 months of initial remission. Many conditioning regimens have been tested, with or without total body irradiation (TBI). Recently, it was found that TBI could be replaced by total marrow irradiation (TMI) using helical tomotherapy, with promising results.This study was a prospective multicenter phase 1 trial that aimed to determine the maximum tolerated dose (MTD) of TMI administered in association with melphalan 140 mg/m², followed by autologous stem cell transplantation as consolidation at first relapse in MM. Four dose levels were explored: 8 Gy, 10 Gy, 12 Gy, and 14 Gy. The dose-limiting toxicity (DLT) was defined as grade 4 neutropenia15 days, grade 4 thrombopenia28 days, and all other grade 4 nonhematologic toxic effects except nausea, vomiting, alopecia, mucositis, and reaction to autologous stem cell infusion.Thirteen patients were included; only 1 DLT at the third escalated dose level (12 Gy) was observed, whereas 1 patient was treated at 14 Gy with no adverse events. The MTD was not reached. The rate of acute toxicity was low: 38% of grade 3-4 diarrhea, mucositis, or unexplained fever. Regarding the lungs, the mean dose administered was systematically less than 8 Gy. After a median follow-up of 55 months, 70% of participants were alive. Of these 13 patients, 38.5% were in very good partial response and 30.8% were in complete response. Three of them were progression-free. Six patients were long survivors, still alive after 55 months of follow-up.Total marrow irradiation provides good results with a good tolerance profile at first relapse in MM and makes it possible to increase the dose delivered to the planning target volume while sparing organs at risk. This technique could be discussed for all regimens before auto- or allo-stem cell rescue when TBI is required.

BackgroundIntensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation.Material and MethodsWe used data from the “RCMI pelvis” prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting.ResultsThe mean total cost for HT, €2019 3,069 (95% CI, 2,885–3,285) was significantly higher than the mean cost for VMAT €2019 2,544 (95% CI, 2,443–2,651) (p ConclusionUse of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis.

Background The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. Patients and methods The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. Results A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. Conclusions In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years., Highlights • A reduction of the number of cancer patients attending cancer centers was observed in France from January to July 2020. • This reduction was observed only for newly diagnosed patients. • The reduction of new diagnosis was more pronounced in women, for breast cancer, and prostate cancer, and nonmetastatic cancer. • No compensation was observed for the last months of 2020. The magnitude of delays may be larger in centers within the same country. • An estimation of the excess cancer death resulting from these delays is presented.

Background: Stereotactic body radiotherapy (SBRT) is a recognized treatment for colorectal cancer (CRC) metastases. We postulated that local responses could be improved by SBRT with a concomitant radiosensitizing agent (irinotecan). Methods: RADIOSTEREO-CAMPTO was a prospective multi-center phase 2 trial investigating SBRT (40&ndash, 48 Gy in 4 fractions) for liver and/or lung inoperable CRC oligometastases (&le, 3), combined with two weekly intravenous infusions of 40 mg/m2 Irinotecan. Primary outcome was the objective local response rate as per RECIST. Secondary outcomes were early and late toxicities, EORTC QLQ-C30 quality of life, local control and overall survival. Results: Forty-four patients with 51 lesions (liver = 39, lungs = 12) were included. Median age was 69 years (46&ndash, 84), 37 patients (84%) had received at least two prior chemotherapy treatments. Median follow-up was 48.9 months. One patient with two lung lesions was lost during follow-up. Assuming maximum bias hypothesis, the objective local response rate in ITT was 86.3% (44/51&mdash, 95% CI: [76.8&ndash, 95.7]) or 82.4% (42/51&mdash, 95% CI: [71.9&ndash, 92.8]). The observed local response rate was 85.7% (42/49&mdash, 95% CI: [75.9&ndash, 95.5]). The 1 and 2-year local (distant) progression-free survivals were 84.2% (38.4%) and 67.4% (21.3%), respectively. The 1 and 2-year overall survivals were 97.5% and 75.5%. There were no severe acute or late reactions. The EORTC questionnaire scores did not significantly worsen during or after treatment. Conclusions: SBRT with irinotecan was well tolerated with promising results despite heavily pretreated patients.

Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy.We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis (NCT01219790). The principal objective was the absence of spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival.Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences).The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects.

Purpose The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years. Patients and Methods Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively (P = .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle. Results At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50). Conclusion At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended.

Purpose There is a scarce clinical experience about adjuvant helical tomotherapy (HT) in patients affected by malignant pleural mesothelioma (MPM) even though it appears as a useful technique to treat complex volume as the pleural cavity, and seems to have better dose distribution than the “classic” intensity modulated radiotherapy (IMRT). Methods and materials Twenty-four patients received adjuvant radiotherapy (RT) by HT from August 1st, 2007 to December 1st, 2009 at Curie Institute (Paris) and Rene Gauducheau Cancer Center (Nantes). Thirteen patients had neoadjuvant chemotherapy. Extrapleural pleuropneumonectomy (EPP) was done in 23 patients. Median dose to PTV was 50 Gy [48.7–55.9 Gy] (2 Gy/fraction). Acute and long term toxicities, disease free survival (DFS), overall survival (OS) and relapses are presented. Results Average follow up after RT was 7 months. The disease was staged mostly as T2–T3, N1–N2. Nineteen patients had epithelial type histology. Most patients tolerated radiotherapy with grade 1–2 side effects: redness of the skin, light cough or dyspnea, fatigue, nausea and odynophagia, mild increase of the post-operative thoracic pain. Grade 3 pneumonitis was suspected in 2 patients. Two grade 5 pneumonitis were also suspected. Eleven patients had a follow up of more than 6 months and no long term side effects related with HT were noted. At 24 months, 51.8% of patients were free of disease. Thirty percent of patients relapsed, with 2 patients presenting local relapses. Two patients died from recurrence. Conclusion With limited follow up, HT has comparable toxicity to those observed with traditional IMRT. Higher radiation dose and good coverage results in excellent local control.

The pooled 2-year clinical experience using three tomotherapy units installed in France in 2007 is presented. Treatment indications and protocols were devised for each disease site and were the result of a consensus. A total of 642 patients were treated for central nervous system, head and neck, thoracic, abdominal, and pelvic tumors. Overall, grade 3, 4, and 5 acute toxicity was 10.7%, 0.3%, and 0.2%, respectively. Grade 3 chronic toxicity was 1.2%. There was no grade 4 or 5 chronic toxicity. The use of tomotherapy in a broad clinical practice is safe, and acute and chronic toxicity both are acceptable for all anatomical locations.

Purpose To determine prospectively intermediate-term toxicity and quality of life (QoL) of prostate cancer patients after intensity-modulated radiotherapy (IMRT). Patients and Methods Fifty-five patients with localized prostate adenocarcinoma were treated by IMRT (76 Gy). Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events version 3.0. Patients assessed general and prostate-specific QoL before IMRT (baseline) and at 2, 6, and 18 months using European Organization for Research and Treatment of Cancer questionnaires QLQ-C30(+3) and QLQ-PR25. Results Median age was 73 years (range, 54–80 years). Risk categories were 18% low risk, 60% intermediate risk, and 22% high risk; 45% of patients received hormonal therapy (median duration, 6 months). The incidence of urinary and bowel toxicity immediately after IMRT was, respectively, 38% and 13% (Grade 2) and 2% and none (Grade 3); at 18 months it was 15% and 11% (Grade 2) and none (Grade 3). Significant worsening of QoL was reported at 2 months with regard to fatigue (+11.31, p = 1.10 −7 ), urinary symptoms (+9.07, p = 3.10 −11 ), dyspnea (+7.27, p = 0.008), and emotional (−7.02, p = 0.002), social (−6.36, p = 0.003), cognitive (−4.85, p = 0.004), and physical (−3.39, p = 0.007) functioning. Only fatigue (+5.86, p = 0.003) and urinary symptoms (+5.86, p = 0.0004) had not improved by 6 months. By 18 months all QoL scores except those for dyspnea (+8.02, p = 0.01) and treatment-related symptoms (+4.24, p = 0.01) had returned to baseline. These adverse effects were exacerbated by hormonal therapy. Conclusion High-dose IMRT with accurate positioning induces only a temporary worsening of QoL.

Helical tomotherapy is an innovative device combining with the same linac on board-imaging and IMRT facilities. The first national French evaluations, supported by National Institut of Cancer (INCa) are presented. Dosimetric characteristics as quality of homogeneity, cut-off outside target volumes allow IMRT treatments for large and complex volumes and a good organ at risk sparing. First comparative dosimetric studies are discussed.

Purpose Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin. Patients and Methods We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m2 twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m2 twice daily 5 days per week and oxaliplatin 50 mg/m2 once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR). Results Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02). Conclusion The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.

The radiosensitizing properties of gemcitabine in relation to low Linear Energy Transfer (LET) particles (Cobalt 60) and high-LET particles (alpha-RIT 213 Bi-radiolabeled CHX-DTPA-B-B4) were analyzed. Three multiple myeloma cell lines (LP1, RPMI 8226, U266) were irradiated with or without 10nM gemcitabine 24h prior to radiation. Gemcitabine led to radiosensitization of LP1 and U266 cells with low-LET (Radiation Enhancement Ratio: 1.55 and 1.49, respectively) but did not radiosensitize any cell line when combined with high-LET.

e22501 Background: To evaluate efficacy and feasibility of radiotherapy (RT: high-level dose 54 Gy, with 30 fractions over / 6 weeks) followed by surgery, for retroperitoneal liposarcomas. Methods: Helical tomotherapy was used for pre-operative RT. Clinical Target Volume (CTV) and main organs at risk were systematically delineated with the surgeon. Surgery was planned 4 to 8 weeks after RT. Inclusion criteria were operable, biopsy-proven, retroperitoneal liposarcomas. Toxicity was graded according to CTCAE V3.0. Overall survival (OS) was estimated using Kaplan-Meier method. Due to competing risks, we estimated the cumulative incidence of loco-regional relapse; 95% confidence intervals are reported [95%CI]. Results: Patients:From 04/2009 to 09/2013, 48 patients were included. Mean age: 62 years (y) (36 to 82). All but 1 patient were OMS ≤ 2. Histological types were 20 well differentiated (WDLS) and 28 dedifferentiated liposarcomas. Mean CTV was 2954 cc. Treatment:1 patient did not have surgery. Dosimetric constraints were respected. Monobloc exerese was systematically achieved. Surgical margins were R0 (16; 34%), R1 (28; 60%), R2 (2; 4%) or missing (1; 2%). Oncological outcomes:Median follow-up was 4.7 y. Cumulative incidence of loco-regional relapse at 3 and 5 y was 17% [8%; 29%] and 31% [16%; 47%] respectively. Estimates were 5% and 35% for dedifferentiated liposarcoma and 26% and 26% for well differentiated liposarcoma. OS at 3 and 5 y was 81% [66%; 89%]) and 78% ([63%; 88%] respectively. Toxicity: 2 months after surgery, 10 grade 3 toxicities and 1 grade 4 toxicity were reported for 6 patients; 3 patients died within 6 months after surgery, 2 of which were related to treatment. After 1 y, no further severe toxicity was observed; 5 cases of second cancers were reported: 1 myeloid leukeamia, 2 pancreatic, 2 breast carcinomas. Conclusions: This trial highlights the feasibility of preoperative 54 Gy RT. Although efficacy data (local control and OS) are encouraging, high incidence rates of acute toxicities and second cancers should be considered. Preoperative RT for WDLS remains questionable. Results from ongoing EORTC phase III Strass trial may provide further level of evidence for this approach. Clinical trial information: NCT01841047.

Purpose: Prognosis of recurrent cancer remains poor, mainly because of the difficulties of achieving a satisfactory local control. Intraoperative radiation therapy (IORT) allows for the delivery of a complementary single dose to the tumor residues or to the tumor bed and could be useful in a multimodal treatment. In an attempt to evaluate this interest, a ertrospective analysis of patients treated with IORT in six French hospitals has bee performed. Methods and Materials: Data have been collected in 73 patients (41 men), with a mean age of 62 years, treated with IORT. Initial rectal tumors were large (mean diameter: 45 mm), partialy or totally fixed to the contiguous structures in 39%, and withnodal involvement in 50% of the cases. Initial surgery had been a sphincter-sparing surgery in 67%; external radiation therapy had been delivered in 52%, and a chemotherapy had been given in 10% of the patients. Recurrences were isolated (without metastases) in 86%, and were posterior or postero-lateral in 55% of the cases. Surgery allowed for a complete macroscopical resection in 57%, a partial resection with gross residual disease in 29%, and no resection in 14% of the recurrences. Intraoperative radiation therapy was delivered in a dose of 10 to 25 Gy (mean 18.5) through localizators of a mean diameter of 75 mm (60 to 110). External radiation therapy, either preoperative or postoeratively was given to 30 patients without prior radiation therapy. Ten patients received additiona chemotherapy with 5-fluorouracil. Results: Four postoperative deaths occurred. Postoperative morbidity occurred in 16 patients and some complications were probably related to the IORT procedure. Four long-term complications were observed. Overall actuarial survival occurred in 72.4% of the patients at year, in 44.6% at 2 years, and 30.6% at 3 years. Twenty-one local failures have been observed. Actuarial local control occurred in 71.3% of the patients at 1 year, 47.7% at 2 years, and 31.3% at 3 years. Conclusion:Intraoperative radiation therapy is a complementary treatment for recurrences of rectal cancer. It provides encouraging results, particularly in some selected situations, when patients have not previously been treated with external radiation therapy. Further studies of multimodal treatmetns are necessary.

Twenty-four patients with T1 or T2 (17 T1 N0, 7 T2 N0 not exceeding 3 cm) epidermoid carcinomas from the middle third of the mobile tongue benefit from brachytherapy with "cavaliers-legos" consisting of guide-gutters that are inserted in a rigid support (legos) and covered with a lead plate. Several advantages can be advocated with this technique: easy implantation even with local anaesthetic, no risk of bleeding, good parallelism between Iridium wires, protection of the mandible with the lead plate. Local control was achieved in 22/24 patients (92%). Four patients (16%) developed soft tissue necrosis but only one required surgical intervention and no mandibular necrosis was seen.

Purpose To evaluate the efficacy and toxicity of high-dose-rate (HDR) brachytherapy in patients with inoperable endobronchial carcinoma. Methods and Materials We retrospectively reviewed the records (April 1991—May 2004) of patients with non–small-cell carcinoma, with no extrabronchial spread on computed tomography scans, who underwent HDR brachytherapy because of contraindications to surgery and external beam radiation therapy. Kaplan-Meier survival curves were compared by the log-rank test. Prognostic factors were analyzed by multivariate analysis. Results 226 patients (223 men, 3 women, mean age: 62.2 years (range, 40–84)) were included. Of those, 217 (97%) had squamous cell carcinoma (Tis/T1/T2/Tx: 60/153/9/4). Dose was prescribed at 1 cm from the radius (24–35 Gy in 4–6 fractions). Mean follow-up was 30.4 months (range, 9–116). Complete endoscopic response rate was 93.6% at 3 months. One hundred twenty-eight patients (56%) died of intercurrent disease ( n = 45), local failure ( n = 36), metastasis ( n = 10), local failure and metastasis ( n = 11), complications ( n = 13), and other causes ( n = 12). The 2-year and 5-year survival rates were, respectively, 57% and 29% (overall) (median, 28.6 months), 81% and 56% (cancer-specific), and 68% and 50% (local disease-free). Acute toxicity included pneumothorax (1.5%) and mucosal inflammation (10%). Late complications were hemoptysis (6.6% with 5% of fatalities), bronchitis (19.5%), and necrosis (3.5%). In multivariate analysis, a distal tumor location and the use of two catheters were associated with improved local disease-free survival ( p = 0.003 and p = 0.007, respectively) and a distal tumor location with improved overall survival ( p = 0.0001). Conclusions This large retrospective study confirms that HDR brachytherapy is an efficient and safe treatment in patients with inoperable endobronchial carcinoma.

Purpose To study the impact of postoperative radiation therapy (PORT) on survival in the Adjuvant Navelbine International Trialist Association (ANITA) randomized study of adjuvant chemotherapy. Methods and Materials ANITA is a randomized trial of adjuvant cisplatin and vinorelbine chemotherapy vs. observation in completely resected non–small-cell lung carcinoma (NSCLC) Stages IB to IIIA. Use of PORT was recommended for pN+ disease but was not randomized or mandatory. Each center decided whether to use PORT before initiation of the study. We describe here the survival of patients with and without PORT within each treatment group of ANITA. No statistical comparison of survival was performed because this was an unplanned subgroup analysis. Results Overall, 232 of 840 patients received PORT (33.3% in the observation arm and 21.6% in the chemotherapy arm). In univariate analysis, PORT had a deleterious effect on the overall population survival. Patients with pN1 disease had an improved survival from PORT in the observation arm (median survival [MS] 25.9 vs. 50.2 months), whereas PORT had a detrimental effect in the chemotherapy group (MS 93.6 months and 46.6 months). In contrast, survival was improved in patients with pN2 disease who received PORT, both in the chemotherapy (MS 23.8 vs. 47.4 months) and observation arm (median 12.7 vs. 22.7 months). Conclusion This retrospective evaluation suggests a positive effect of PORT in pN2 disease and a negative effect on pN1 disease when patients received adjuvant chemotherapy. The results support further evaluation of PORT in prospectively randomized studies in completely resected pN2 NSCLC.

High Dose Hypofractionated Stereotactic Body Radiation Therapy of Non Compressive Vertebral Bone Metastases in Combination With Zoledronic Acid: A Phase 1 Study B. Pichon, M.A. Mahe, G. Delpon, F. Thillays, C. Carrie, P. Cellier, P. Pommier, C. Laude, A. Mervoyer, and S. Supiot; ICO, Nantes Saint Herblain, France, Department of Radiation Oncology, ICO, Nantes Saint Herblain, France, CRCNA, Inserm U892, CNRS UMR 6299, Nantes Saint Herblain, France, Centre Leon Berard, Lyon, France, Department of Radiation Oncology, ICO, Angers, France, Department of Radiation Oncology, Leon Berard, Lyon, France

2054 Background: BM, the most frequent malignancy in the central nervous system, remains of poor prognosis. Standard treatment is WBRT. Neo-angiogenesis plays an important role in BM growth. Angiog...

Purpose: To report long-term pulmonary, thyroid, and ocular complications in patients who had conditioning regimens including total body irradiation (TBI) before bone marrow transplantation (BMT). Methods and Materials: Between June 1986 and December 1995, 478 patients received TBI in our institution. The present study includes 186 adult patients who had complete remission lasting one year or more after BMT. There were 108 males and 78 females. Median age was 36.5 years (range 15–60). Initial diagnoses were lymphomas (50%), acute lymphoid leukemias (16%), acute myeloid leukemias (16%), chronic myeloid leukemia (13%), aplastic anemia (3%), and myelodysplasia (2%). At the time of BMT, 43.5% of patients were in complete response and 56.5% in partial response. Treatment consisted of a single dose TBI at 10 Gy in 9% and fractionated TBI delivering 12 to 13.5 Gy in 6 fractions in 91%. From 1986 to October 1991, TBI was performed in lateral position with 9 MV energy (57% of patients) and thereafter in alternate prone and supine positions with 15 MV energy (43%). Chemical conditioning regimen was cyclophosphamide (60 mg/kg at D-4 and D-3) in 69% and CBV (cyclophosphamide 1500 mg/m 2 from D-6 to D-3, BCNU 300 mg/m 2 at D-6, VP-16 200 mg/m 2 from D-6 to D-4) in 25%. Fifty eight percent of patients received autologous and 42% allogeneic BMT. All patients had clinical, biologic, and functional examinations at one-year intervals. Results: Median follow-up from BMT was 49 months (range 12–136). Late pulmonary effects were observed only in functional explorations, without clinical effect, including restrictive syndrome in 8% and alteration in the diffusing capacity of carbon monoxide in 12%. No patient showed clinical thyroid symptoms, and 10% developed biologic dysfunction: hypothyroidism (6.5%), thyroiditis (3%), and Basedow disease (0.5%). Ocular complications occurred in 29.5%, including cataract (15%), dry syndrome (13%), and keratitis (1.5%). In univariate and multivariate analysis, pulmonary complications were statistically increased by chronicle graft vs. host disease (GVHD) vs. no ( p = 0.02), prone and supine vs. lateral TBI position ( p = 0.02), and with 15 MV vs. 9 MV beam energy ( p = 0.02). Cataract occurred less frequently with fractionated than with single-dose TBI ( p = 0.000002). No differences were observed regarding age, sex, initial diagnosis, status at the time of BMT, conditioning chemotherapy regimen, and total dose of TBI. Conclusion: From this retrospective study it was shown that long-term complications of TBI were not symptomatic in most patients. The role of parameters of irradiation and especially position of treatment and beam energy should be emphasized and assessed with a longer follow-up.

Purpose: To evaluate the efficacy of total abdominopelvic (TAI) and total body irradiation (TBI) in heavily pretreated follicular non-Hodgkin’s lymphoma (NHL). Patients and Methods: From 1983 to 1998, 34 patients received TAI ( n = 22) or TBI ( n = 12). All had Stage III or IV, Class B, C, D NHL in the working formulation and failed after receiving 1–5 regimens of chemotherapy. TAI was given at 20 Gy over a 3-week period. TBI was delivered in two successive half-body irradiations of 15 Gy over a 2-week period with a 4-week interval between each. Results: Mean follow-up from TAI or TBI was 120 months (range, 6–180). Seventy-six percent of patients achieved complete response and 24% partial response. Median survival was 62 months, 5-year and 10-year overall survival was 59% and 41%, and disease-free survival was 56% and 30%, respectively. Grade III or IV toxicity was gastrointestinal in 38% of patients and hematologic in 30%. No toxic death or delayed complications were observed. Conclusion: Extended-field irradiation is feasible and efficient after failure of chemotherapy in follicular NHL.

Thirty-five adult patients with high-risk HD (HD) defined by (1) Ann Arbor stage IV or bulky nodal disease (tumor/thorax ratio > 0.45) and (2) no or partial response (PR) (< 75%) to the initial 3 courses of ABVD, received an early intensive therapy with autologous stem cell transplantation (ASCT). Thirty patients were considered as partial responders and 5 as refractory to initial chemotherapy. Conditioning regimen consisted of chemotherapy alone (CBV in 11 patients before 1993, BEAM in 13 patients since 1993) followed by adjuvant radiotherapy: 40 Gy) on the initial sites of bulky disease, or 12 Gy total body irradiation plus 120 mg/kg cyclophosphamide in 11 patients with disseminated extra-nodal disease. All 30 patients in PR at the time of ASCT experienced prolonged complete remission (CR). One patient died in CR from an acute myocardial infarction 48 months after ASCT. Four out of the 5 patients with refractory disease at the time of ASCT experienced rapid progression of HD leading to death in 3 cases. After 6 years of CR post-ASCT, the last refractory patient died of myelodysplastic syndrome diagnosed 2 years after intensive therapy. With a median follow-up for surviving patients of 51 months (range: 11-111), the cumulative probability of 8-year overall survival is 75.6% for the entire group of patients, 94.1% for the chemosensitive ones, and 0% for the primary refractory (P < .0001). The cumulative probability of 8-year event-free survival is 79.9% for the entire group of patients, 94.1% for the chemosensitive ones, and 0% for the primary refractory (P < .0001). We conclude that early intensive therapy with ASCT is feasible in patients with high-risk HD and induces a high cure rate in chemosensitive patients. In primary refractory patients, new therapeutic approaches are warranted.

To evaluate the therapeutic efficacy of moderate-dose total abdominopelvic irradiation (TAI) in a retrospective series of pretreated non-Hodgkin's lymphomas (NHL).From 1977 to 1994, 45 patients received TAI after failure of chemotherapy (CT). According to the Working Formulation, 10 patients were diagnosed with class A (group I), 19 with class B, C, or D (follicular) (group II), and 16 with class E or more severe (group III) NHL. Irradiation consisted of two daily fractions of 0.80 Gy each for a total dose of 20 Gy.Mean follow-up after TAI was 102 months (range 8-156). For the entire group, the complete response (CR) rate was 66%, the partial response (PR) rate 29%, 10-year overall survival (OS) 35%, 10-year disease-free survival (DFS) 29%, and median survival 32 months. When results between subgroups were compared, CR was 70% in group I, 84% in group II, and 44% in group III; and survival was statistically higher in group II than in groups I and III: 10-year OS 52% vs. 10% (p0.01) and 31% (p0.05), respectively, 10-year DFS 37% vs. 10% (p0.03) and 19% (p0.05), respectively. Grade III or IV complications were gastrointestinal in 27% of patients and hematologic in 25%.Large-field irradiation in moderate doses could provide an alternative to bone marrow transplantation in refractory NHL, especially in cases showing a follicular growth pattern.

To develop novel biomarkers of rectal radiotherapy, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy.Six patients presenting with a locally advanced rectal cancer (TT2, N0/Nx, M0) eligible for preoperative radiotherapy (45 Gy in 25 fractions) were selected in a pilot study. Six tumor and 3 normal tissues biopsies were taken before and during radiotherapy, after a dose of 7.2 Gy at a median time of 1 h following irradiation (0:27-2:12). Tumor or normal tissue purity was assessed by a pathologist prior to RNA extraction. Mean RNA content was 23 μg/biopsy (14-37) before radiotherapy and 22.7 μg/biopsy (12-35) during radiotherapy. After RNA amplification, biopsies were analysed with 54K HG-U133A Plus 2.0 Affymetrix expression micro-arrays. Data were normalized according to MAS5 algorithm. A gene expression ratio was calculated as: (gene expression during radiotherapy - gene expression before radiotherapy)/gene expression before radiotherapy. Were selected genes that showed a ratio higher than ± 0.5 in all 6 patients.Microarray analysis showed that preoperative radiotherapy significantly up-regulated 31 genes and down-regulated 6 genes. According to the Gene Ontology project classification, these genes are involved in protein metabolism (ADAMDEC1; AKAP7; CAPN5; CLIC5; CPE; CREB3L1; NEDD4L; RAB27A), ion transport (AKAP7; ATP2A3; CCL28; CLIC5; F2RL2; NEDD4L; SLC6A8), transcription (AKAP7; CREB3L1; ISX; PABPC1L; TXNIP), signal transduction (CAPN5; F2RL2; RAB27A; TNFRSF11A), cell adhesion (ADAMDEC1; PXDN; SPON1; S100A2), immune response (CCL28; PXDN; TNFRSF11A) and apoptosis (ITM2C; PDCD4; PVT1). Up-regulation of 3 genes (CCL28; CLIC5; PDCD4) was detected by 2 different probes and up-regulation of 2 genes (RAB27A; TXNIP) by 3 probes.Micro-arrays can efficiently assess early transcriptomic changes during preoperative radiotherapy for rectal cancer, and may help better understand tumor radioresistance.

Purpose : To evaluate the feasibility and oncologic results of intraoperative radiation therapy (IORT) for recurrent uterine cervical carcinoma in a cohort of patients treated in seven French institutions. Methods and Materials : From 1985 to 1993, 70 patients with pelvic recurrences underwent IORT with/ without external radiation therapy (ERT) and chemotherapy (CT). Treatment modalities for recurrence were IORT alone (40 out of 70), IORT + ERT (30 out of 70), additional chemotherapy (20 out of 70). Gross complete resection (CR) was performed in 30 out 70 cases, partial resection (PR) in 37 out of 70, and unspecified surgery in 3 out of 70. Sixty-five patients had electron beam IORT and 5,100 KV photon IORT. Mean IORT cone size, electron beam energy, and dose (calculated at the 90% isodose line) were, respectively, 75 mm (40 to 90), 12 MeV (6 to 20), and 18 Gy (10 to 25) after CR and 80 mm (45 to 100), 15 MeV (7 to 24), and 19 Gy (10 to 30) after PR. Mean follow-up after IORT was 15 months (2 to 69). One, 2- and 3-year overall survival rates were 47, 17 and 8%, respectively; median survival was 11 months and local control, 21%. Median survival and local control rates increased after CR (13 moths, 27%) vs. PR (10 months, 17%) and when initial treatment consisted surgery (S) alone (15 months, 25%) vs. radiation therapy (RT ± S) (10 months, 16%). However, these differences were not statistically significant. No death-related toxicity was observed. Grade 2 or 3 toxicity was observed in 19 out of 70 patients (27%), including 9 not directly IORT-related complications (13%) (three digestive tract fistulas, one rectal stricture, three urinary fistulas, two infections) and 10 directly IORT-related complications (14%) (five neuropathies, four ureteral obstructions, and one rectal stricture). Conclusion : This retrospective study demonstrates the feasibility of IORT. The usefulness of IORT still needs to be evaluated in primary treatment of advanced stages of cervical carcinoma.

151 Background: To determine prospectively long-term toxicity and quality of life (QoL) of prostate cancer patients after intensity-modulated radiotherapy (IMRT). Methods: 55 patients with localized prostate adenocarcinoma were treated by IMRT (76 Gy) between February and November 2006. Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events version 3.0. Patients assessed general and prostate-specific QoL before IMRT (baseline) and at 2, 18 and 54 months using European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-PR25. Results: Median age was 73 years (range 54-80 years). Risk categories were 18% low risk, 60% intermediate risk, and 32% high risk. The incidence of urinary and bowel toxicity immediately after IMRT (n=55) was, respectively, 36.8% and 23.7% (grade 1), 5.3% and 5.3% (grade 2), 2.6% and none (grade 3). At 18 months (n=55), it was 23.7% and 10.3% (grade 1), 26.3% and 13.2% (grade 2) and none and 2.6% (grade 3). At 54 months (n=38), it was, 34.2 and 23.7% (grade 1), 5.3% and 15.8% (grade 2) and 5.3% and none (grade 3). After 54 months, there was a statistically significant worsening of QoL with regards to 11 items among the 19 studied. However, the scores were clinically relevant (decrease > 10 points) only for physical functioning, role functioning, social functioning, fatigue, pain, dyspnea and constipation. No statistical differences were shown between 54 months and baseline for general health, bowel symptom, treatment related symptoms and sexual activity. Concerning urinary symptoms, there was a statistically significant deterioration but not clinically relevant (difference < 10 points). Conclusions: High-dose IMRT to the prostate with accurate positioning does not induce any clinically relevant deterioration in long-term urinary and gastrointestinal QoL. Deterioration in functioning items may also be related to age and comorbidities. To our knowledge, our study is the only prospective study regarding quality of life following prostate IMRT with a very long follow-up of 54 months.

9549 Background: In head-and-neck rhabdomyosarcoma (RMS), radiotherapy have an important place because tumors are rarely available to complete surgical resection. Intensity-modulated- radiotherapy ...

7579 Background: This phase II clinical study was conducted to evaluate the effectiveness of the association of extrapleural pneumonectomy followed by radiation therapy in patients with potentially resectable malignant pleural mesothelioma (MPM). Methods: Eligible patients had histologically proven epithelial or mixed MPM with clinical stage T1–3, N0–2, M0 disease considered to be completely resectable and a WHO performance status of 0 or 1. Surgery had to consist of a complete extrapleural pneumonectomy including resection of pericardium and diaphragm. Postoperative radiotherapy (40 Gy) was delivered through anterior and posterior fields, with a 10 to 20 Gy boost dose if necessary. Results: Thirty seven patients were included in this study. Extrapleural pneumonectomy was completed in 35 patients. Overall hospital mortality was 5,7 %. Major post operative complications were: 3 acute lung injury, 1 bronchopleural fistula, 1 stroke, 1 chylothorax and one diaphragmatic patch dehiscence. IMIG post-operative staging was: stage II = 5 patients; stage III = 25 patients; stage IV = 5 patients. Adjuvant radiation was administered to 29 patients. Survival for the 35 patients with complete resection was 47 ± 8 % at 2 years. Median overall survival time was 22 months. Survival without recurrence was 37 ± 8 % at 2 years. Median time to progression was 15 months. Locoregional recurrence is the most common form of relapse. Conclusions: In the era of surgical neoadjuvant therapy in MPM treatment, extrapleural pneumonectomy followed by radiation therapy in patients with resectable epithelial or mixed MPM can achieve acceptable results. No significant financial relationships to disclose.

7688 Objective: To evaluate efficacy and toxicity of HDR BT in non operable endobronchial carcinoma from a retrospective multicentric study. Patients and Methods: Criteria for selection: non small cell carcinoma accessible to fiberoptic bronchoscopy, no extrabronchial extension on CT, contraindication to surgery and external radiation therapy (ERT). Statistical analysis: survival curves calculated with the Kaplan-Meier method and compared with the Logrank test; Cox model to evaluate in uni and multivariate analysis the impact on survival and complications of these parameters: location of tumor: lobar or segmental vs main stem bronchus, previous ERT vs no, total dose:= 30 Gy vs less, dose per fraction:= 5 Gy vs more, number of catheter(s):1 vs = 2. Results: Between 1991 and 2006, 226 patients from 9 radiotherapy departments were included. Main characteristics of tumors: squamous-cell histology: 96%, stage Tis: 60, T1: 153, T2: 9, Tx 4; lobar or segmental location: 91%. 51 patients (22.5%) had received ERT for previous lung cancer(s). Characteristics of HDR BT were: total dose = 30 Gy: 70%, dose per fraction = 5 Gy: 66%, 1 catheter: 46%. Dose was prescribed at 1 cm from the radius. Mean follow-up was 30.4 months (9- 116). Histologic evaluation was performed at 3 months in 137 patients. 92% had a complete response. 128 patients were died: intercurrent disease 45, local failure 35, complications 13. Two and 5-year survival: overall: 57%, 29%; specific (death of lung cancer) 81%, 56%; local- relapse free (LRF) 68%, 50%. Toxicity included 1.3% pneumothorax, hemoptysis 6.6% (5% fatal), bronchitis 20%. In univariate analysis: overall, specific and LRF survival were better for lobar or segmental location vs main stem bronchus (p=0.0001), overall and specific survival were higher with no previous ERT (p=0.006). In multivariate analysis, lobar or segmental location was associated with improved overall (p=0.0001) and LRF (p=0.003) survival. LRF survival was better in patients treated with = 2 catheters (p=0.007). No factor influence frequency of complications. Conclusion: This large retrospective study confirmed that HDRBT is efficient and safe in medically inoperable patients particulary with lobar or segmental endobronchial carcinoma. No significant financial relationships to disclose.