A Multicenter Phase 2 Study of Ultrahypofractionated Stereotactic Boost After External Beam Radiotherapy in Intermediate-risk Prostate Carcinoma: A Very Long-term Analysis of the CKNO-PRO Trial.

Background: Genitourinary (GU) or gastrointestinal (GI) complications and tumor relapse can occur in the long term after radiotherapy for prostate cancer. Objective: To assess the late tolerance and relapse-free survival (RFS) in patients undergoing hypofractionated stereotactic boost therapy after external beam radiotherapy (EBRT) for intermediate-risk prostate cancer. Design setting and participants: Seventy-six patients with intermediate-risk prostate carcinoma between August 2010 and April 2013 were included. The first course delivered a dose of 46 Gy by conventional fractionation; the second course was a boost of 18 Gy (3 × 6 Gy) within 10 d. Outcome measurements and statistical analysis: GU and GI toxicities were evaluated as the primary outcomes. The secondary outcomes were overall survival and RFS. The cumulative incidence of toxicity was calculated using a competing-risk approach. Overall survival and RFS were estimated using the Kaplan-Meier method. Results and limitations: The median follow-up period was 88 mo (range, 81-99 mo). Sixty (79%) patients were treated with the CyberKnife and 16 (21%) using a linear accelerator. The cumulative incidences of GU and GI grade ≥2 toxicities at 120 mo were 1.4% (95% confidence interval [CI]: 0.1-6.6%) and 11.0% (95% CI: 5.1-19.4%), respectively. The overall survival and RFS rates at 8 yr were 89.1% (95% CI: 77-95%) and 76.9% (95% CI: 63.1-86.1), respectively. Conclusions: A very long follow-up showed low GU and GI toxicities after a hypofractionated stereotactic boost after EBRT for intermediate-risk prostate cancer. Dose escalation of the boost delivered by hypofractionated radiation therapy appears safe for use in future trials. Patient summary: We found low toxicity and good survival rates after a short and high-precision boost after external beam radiotherapy for intermediate-risk prostate cancer, with a long-term follow-up of 88 mo. This long-term treatment is safe and should be considered in future trials.

Stereotactic focal radiotherapy as an alternative treatment for low-risk prostate cancer: Results of a single-arm monocenter Phase-II trial.

Introduction: Since radical treatments in low risk prostate cancer do not improve overall survival in comparison to active surveillance, preserving quality of life (QOL) remains the key objective. Active surveillance of indolent prostate cancer avoids curative treatment side-effects but necessitates repeated biopsies. Focal stereotactic body radiation therapy (focal SBRT) may be an alternative. This non-randomized Phase-II trial examined the feasibility and safety of focal SBRT for low and favorable intermediate-risk prostate cancer. Methods: Patients were recruited in 2016-2019 if they had: localized CAPRA ≤ 3 prostate adenocarcinoma; an isolated PIRADS≥4 macroscopic tumor on MRI; WHO Performance Status 0-1; and no major urinary symptoms. 36.25 Gy (80% isodose prescription) were delivered in 5 fractions every other day. Primary outcome was delay between focal SBRT and salvage-treatment initiation. Secondary outcomes were: acute/late genitourinary/rectal toxicity; biological, clinical and MRI local control; and change in QOL measures. Results: Over a median follow-up of 36 months, salvage prostatectomy in the 24 eligible patients was never required. Three-year biochemical progression-free survival was 96%. The single biochemical recurrence was a small (2-mm) Gleason 6 (3 + 3) lesion in the non-irradiated lobe. All 19 patients with ≥1 post-treatment MRI evaluations demonstrated complete radiological response. Acute/late grade ≥3 toxicities did not occur: all acute toxicities were grade-1 genitourinary (38% patients), grade-2 genitourinary (8%), or grade-1 rectal (13%) toxicities. There was one (4%) late grade-1 genitourinary toxicity. QOL was unchanged at last follow-up, as shown by IPSS (2.86 to 3.29, p>0.05), U-QOL (0.71 to 0.67, p>0.05), and IIEF5 (the 14 initially potent patients maintained potency (IIEF5 > 16)). Conclusion: Focal SBRT is feasible, well-tolerated, and preserves QOL. This innovative robotized approach challenges active surveillance.

Prospective validation of stringent dose constraints for prostatic stereotactic radiation monotherapy: results of a single-arm phase II toxicity-oriented trial.

PURPOSE: There are no safety-focused trials on stereotactic body radiotherapy (SBRT) for localized prostate cancer. This prospective 3­year phase II trial used binomial law to validate the safety and efficacy of SBRT with stringent organ at risk dose constraints that nevertheless permitted high planning target volume doses. METHODS: All consecutive ≥ 70-year-old patients with localized prostate adenocarcinoma who underwent SBRT between 2014 and 2018 at the National Radiotherapy Center in Luxembourg were included. Patients with low Cancer of Prostate Risk Assessment (CAPRA) scores (0-2) and intermediate scores (3-5) received 36.25 Gy. High-risk (6-10) patients received 37.5 Gy. Radiation was delivered in 5 fractions over 9 days with Cyberknife-M6™ (Accuray, Sunnyvale, CA, USA). Primary study outcome was Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) genitourinary and rectal toxicity scores at last follow-up. Based on binomial law, SRBT was considered safe in this cohort of 110 patients if there were ≤ 2 severe toxicity (CTCAEv4 grade ≥ 3) cases. Secondary outcomes were biochemical progression-free survival (bPFS) and patient quality of life (QOL), as determined by the IPPS and the Urinary Incontinence QOL questionnaire. RESULTS: The first 110 patients who were accrued in a total cohort of 150 patients were included in this study and had a median follow-up of 36 months. Acute grade ≥ 3 toxicity never occurred. One transient late grade 3 case was observed. Thus, our SBRT program had an estimated severe toxicity rate of < 5% and was safe at the p < 0.05 level. Overall bPFS was 90%. QOL did not change relative to baseline. CONCLUSION: The trial validated our SBRT regimen since it was both safe and effective.

Tumor Size Matters-Understanding Concomitant Tumor Immunity in the Context of Hypofractionated Radiotherapy with Immunotherapy.

The purpose of this study was to determine the dynamic contributions of different immune cell subsets to primary and abscopal tumor regression after hypofractionated radiation therapy (hRT) and the impact of anti-PD-1 therapy. A bilateral syngeneic FSA1 fibrosarcoma model was used in immunocompetent C3H mice, with delayed inoculation to mimic primary and microscopic disease. The effect of tumor burden on intratumoral and splenic immune cell content was delineated as a prelude to hRT on macroscopic T1 tumors with 3 fractions of 8 Gy while microscopic T2 tumors were left untreated. This was performed with and without systemic anti-PD-1. Immune profiles within T1 and T2 tumors and in spleen changed drastically with tumor burden in untreated mice with infiltrating CD4+ content declining, while the proportion of CD4+ Tregs rose. Myeloid cell representation escalated in larger tumors, resulting in major decreases in the lymphoid:myeloid ratios. In general, activation of Tregs and myeloid-derived suppressor cells allow immunogenic tumors to grow, although their relative contributions change with time. The evidence suggests that primary T1 tumors self-regulate their immune content depending on their size and this can influence the lymphoid compartment of T2 tumors, especially with respect to Tregs. Tumor burden is a major confounding factor in immune analysis that has to be taken into consideration in experimental models and in the clinic. hRT caused complete local regression of primary tumors, which was accompanied by heavy infiltration of CD8+ T cells activated to express IFN-γ and PD-1; while certain myeloid populations diminished. In spite of this active infiltrate, primary hRT failed to generate the systemic conditions required to cause abscopal regression of unirradiated microscopic tumors unless PD-1 blockade, which on its own was ineffective, was added to the RT regimen. The combination further increased local and systemically activated CD8+ T cells, but few other changes. This study emphasizes the subtle interplay between the immune system and tumors as they grow and how difficult it is for local RT, which can generate a local immune response that may help with primary tumor regression, to overcome the systemic barriers that are generated so as to effect immune regression of even small abscopal lesions.

A Multicenter Phase 2 study of Hypofractionated Stereostatic Boost in Intermediate Risk Prostate Carcinoma: A 5-Year Analysis of the CKNO-PRO Trial.

PURPOSE: The aim of this analysis was to assess the 5-year tolerance and survival in patients undergoing hypofractionated stereotactic boost after external beam radiation therapy (EBRT) for intermediate-risk prostate cancer. METHODS AND MATERIALS: Between August 2010 and April 2013, 76 patients with intermediate-risk prostate carcinoma were included in the study. A first course delivered 46 Gy using conventional fractionation. The second course delivered a boost of 18 Gy (3 × 6 Gy) within 10 days using stereotactic body radiation therapy (SBRT). Gastrointestinal and genitourinary toxicities were assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.0. Secondary outcome measures were overall, biochemical relapse-free, and relapse-free survival; prostate-specific antigen kinetics; and patient functional status (urinary and sexual) according to the International Index of Erectile Function and International Prostate Symptom Score questionnaires. RESULTS: Sixty patients (79%) were treated by CyberKnife and 16 (21%) by linear accelerator. Median follow-up was 62 months (range, 29-69). The cumulative incidence of genitourinary and gastrointestinal grade ≥2 toxicities at month 60 after the end of radiation therapy was 1.4% (95% confidence interval [CI], 0.1%-6.6%) and 9.3% (95% CI, 4.1%-17.1%), respectively. Biochemical relapse-free and relapse-free survival rates at 5 years were 87.4% (95% CI, 77.1%-93.2%) and 86.2% (95% CI, 75.8-92.3), respectively. The mean (standard deviation) prostate-specific antigen variation within 3 months and 5 years post-radiation therapy was -1.20 ng/mL/mo (0.79) and -1.30 ng/mL/y (1.05), respectively. There was no significant difference between the International Prostate Symptom quality of life score between inclusion and month 60. For the International Index of Erectile Function, there was a significant difference between inclusion and month 60 (P = .005), with a higher proportion of severe/noninterpretable disorders at 60 months. CONCLUSIONS: The results of the trial demonstrate that the EBRT and SBRT combination is well tolerated and yields good efficacy results. These data provide a good basis for comparing EBRT and brachytherapy boost to EBRT and SBRT boost in future prospective studies.

Salvage Stereotactic Body Radiation Therapy for Local Prostate Cancer Recurrence After Radiation Therapy: A Retrospective Multicenter Study of the GETUG.

PURPOSE: To assess the efficacy and safety of salvage stereotactic body radiation therapy (SBRT) in patients with biopsy-proven local prostate cancer recurrence after radiation therapy. METHODS AND MATERIALS: Between April 2010 and January 2017, 100 patients were included in 7 centers. Disease extension was assessed by pelvic multiparametric magnetic resonance imaging and choline positron emission tomography in 87% and 94% of patients, respectively. The median time interval between the 2 treatments was 7.5 years (range, 2-18). Median prostate-specific antigen at recurrence was 4.3 ng/mL (range, 2-38). Median SBRT dose was 36 Gy (range, 25-36.25) in 6 fractions (range, 5-6), every other day. Thirty-four percent of patients were treated by androgen deprivation therapy for a median duration of 12 months. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03. RESULTS: Median follow-up was 29.3 months (range, 4-91). Second biochemical recurrence-free survival rate at 3 years was 55% (95% confidence interval [CI], 42%-66%). The initial D'Amico group, time interval after first radiation therapy, and SBRT dose were prognostic factors of biochemical recurrence-free survival in multivariate analysis (P = .09, P = .025, P = .018, respectively). No patient developed acute gastrointestinal toxicity of grade >1; rates of acute genitourinary toxicity of grade 2 and 3 were 8% and 1%, respectively. The actuarial 3-year grade ≥2 genitourinary and gastrointestinal toxicity was 20.8% (95% CI, 13%-29%) and 1% (95% CI, 0.1%-5.1%), respectively. One patient presented with neuritis of grade 3. CONCLUSIONS: With a short follow-up, this study shows that salvage SBRT allows for encouraging control and acceptable toxicity. Further prospective studies are necessary to confirm these preliminary results and to determine late toxicity.

Irradiation to Improve the Response to Immunotherapeutic Agents in Glioblastomas.

PURPOSE: Glioblastoma (GBM) remains an incurable disease despite extensive treatment with surgical resection, irradiation, and temozolomide. In line with many other forms of aggressive cancers, GBM is currently under consideration as a target for immunotherapy. However, GBM tends to be nonimmunogenic and exhibits a microenvironment with few or no effector T cells, a relatively low nonsynonymous somatic mutational load, and a low predicted neoantigen burden. GBM also exploits a multitude of immunosuppressive strategies. METHODS AND MATERIALS: A number of immunotherapeutic approaches have been tested with disappointing results. A rationale exists to combine immunotherapy and radiation therapy, which can induce an immunogenic form of cell death with T-cell activation and tumor infiltration. RESULTS: Various immunotherapy agents, including immune checkpoint modulators, transforming growth factor beta receptor inhibitors, and indoleamine-2,3-dioxygenase inhibitors, have been evaluated with irradiation in preclinical GBM models, with promising results, and are being further tested in clinical trials. CONCLUSIONS: This review aims to present the basic rationale behind this emerging complementary therapeutic approach in GBM, appraise the current preclinical and clinical data, and discuss the future challenges in improving the antitumor immune response.

NHL-ChirEx: An interprofessional cross-border education initiative in the Greater Region with a focus on radiation morbidity and patient safety.

NHL-ChirEx is an interprofessional cross-border education project that addresses the potential excess of radiation induced morbidity throughout the radiation planning and treatment process. NHL-ChirEx is supported by ESTRO and the University of the Greater Region and has been recently approved and funded under INTERREG VA Programme.

Hypofractionated stereotactic boost in intermediate risk prostate carcinoma: Preliminary results of a multicenter phase II trial (CKNO-PRO).

PURPOSE: Dose escalation may improve curability in intermediate-risk prostate carcinoma. A multicenter national program was developed to assess toxicity and tumor response with hypofractionated stereotactic boost after conventional radiotherapy in intermediate-risk prostate cancer. METHODS AND MATERIAL: Between August 2010 and April 2013, 76 patients with intermediated-risk prostate carcinoma were included in the study. A first course delivered 46 Gy by IMRT (68.4% of patients) or 3D conformal radiotherapy (31.6% of patients). The second course delivered a boost of 18 Gy (3x6Gy) within 10 days. Gastrointestinal (GI) and genitourinary (GU) toxicities were evaluated as defined by NCI-CTCAE (v4.0). Secondary outcome measures were local control, overall and metastasis-free survival, PSA kinetics, and patient functional status (urinary and sexual) according to the IIEF5 and IPSS questionnaires. RESULTS: The overall treatment time was 45 days (median, range 40-55). Median follow-up was 26.4 months (range, 13.6-29.9 months). Seventy-seven per cent (n = 58) of patients presented a Gleason score of 7. At 24 months, biological-free survival was 98.7% (95% CI, 92.8-99.9%) and median PSA 0.46 ng/mL (range, 0.06-6.20 ng/mL). Grade ≥2 acute GI and GU toxicities were 13.2% and 23.7%, respectively. Grade ≥2 late GI and GU toxicities were observed in 6.6% and 2.6% of patients, respectively. No grade 4 toxicity was observed. CONCLUSIONS: Hypofractionated stereotactic boost is effective and safely delivered for intermediate-risk prostate carcinoma after conventional radiation. Mild-term relapse-free survival and tolerance results are promising, and further follow-up is warranted to confirm the results at long term. TRIAL REGISTRATION: ClinicalTrials.gov NCT01596816.

A retrospective cohort study to assess adjuvant concurrent chemoradiation (CCRT) compared to adjuvant radiation therapy (RT) in the treatment of grade 2 and 3 extremity soft tissue sarcomas.

PURPOSE: To evaluate the efficacy and tolerance of adjuvant concurrent chemoradiation (CCRT) as treatment of grade 2 and 3 (G2-3) localized extremity soft tissue sarcomas (STS) by comparing CCRT with standard adjuvant radiation therapy (RT). PATIENTS AND METHODS: This monocentric retrospective study included non-pediatric patients (>16years) treated by adjuvant RT with or without chemotherapy (CT) after conservative resection of non-recurrent G2-3 extremity STS. RESULTS: A total of 80 patients were treated between 1990 and 2012: 51 by RT and 29 by CCRT. Of the 29 CCRT patients, 25 received doxorubicin monotherapy (75mg/m2/3weeks). The CCRT group contained a greater proportion of grade 3 extremity STS (p<0.001). Median follow up was 68months (9-284). Multivariate analysis revealed greater local control in the CCRT group (1 local recurrence vs 8 in the RT group; HR=0.082, 95% CI 0.011-0.321) and incomplete resection as the major risk factor of local recurrence (HR=25.2, 95% CI 4.767-133.226). The two groups exhibited no differences in distant failure-free survival (HR=1.469, 95% CI 0.668-3.228), disease-free survival (HR=1.096, 95% CI 0.519-2.315) or overall survival (HR=1.378, 95% CI 0.498-3.814). Grade 3 was an adverse prognostic factor for overall survival (HR=3.11, 95% CI 1.04-9.32). Our analyses also revealed that CCRT tended to increase the risk of both grade ≥3 acute dermatitis (14 events vs 6 in the RT group; OR=6.99, 95% CI 2.28-21.47) and grade ≥2 late toxicity (6 events vs 3 in the RT group; p=0.0572). CONCLUSION: CCRT could improve local control as part of a limb-preservation strategy. However, with a limited number of patients, CCRT showed no improvement in either distant control or survival and increased toxicity.

Salvage robotic SBRT for local prostate cancer recurrence after radiotherapy: preliminary results of the Oscar Lambret Center.

BACKGROUND: Currently, there is no standard option for local salvage treatment for local prostate cancer recurrence after radiotherapy. Our objective was to investigate the feasibility and efficiency of Robotic Stereotactic Body Radiation Therapy (SBRT) in this clinical setting. METHODS/MATERIALS: We retrospectively reviewed patients who were treated at our institution with SBRT for local prostate cancer recurrence after External Beam Radiation Therapy (EBRT) or brachytherapy. Multidisciplinary staff approved the treatment, and recurrence was biopsy-proven when feasible. A dose of 36 Gy was prescribed in six fractions. Treatment was delivered every other day. RESULTS: Between August 2011 and February 2014, 23 patients were treated with SBRT for intra-prostate cancer recurrence with a median follow up of 22 months (6 to 40). Twenty patients had biopsy-proven recurrence. For 19 patients, EBRT was the initial treatment and in four patients, brachytherapy was the initial treatment; the median relapse-time from initial treatment was 65 months (28 to 150). At relapse, 10 patients had an extra-capsular extension. Fourteen patients were treated with androgen deprivation that could be stopped after a median of 1 month after SBRT (range 0-24). A PSA decrease occurred in 82.6% of the patients after SBRT. The 2-year disease-free survival and overall survival rates were 54 and 100%, respectively. Disease progression was observed for nine patients (39.1%) (five local, three metastatic and one nodal progression) after a median of 20 months (7-40 months). The median nadir PSA was 0.35 ng/ml and was achieved after a median of 8 months (1 to 30) after treatment. We observed no grade 4 or 5 toxicity. Two patients presented with grade 3 toxicities (two Cystitis and one neuralgia). Other toxicities included urinary toxicities (five grade 2 and nine grade 1) and rectal toxicities (two grade 2 and two grade 1). CONCLUSION: SBRT for local prostate cancer recurrence seems feasible and well tolerated with a short follow up. Prospective evaluation is needed.

Safety of adjuvant intensity-modulated postoperative radiation therapy in endometrial cancer: Clinical data and dosimetric parameters according to the International Commission on Radiation Units (ICRU) 83 report.

AIM: To report a single-institution experience using postoperative pelvic Intensity Modulation Radiation Therapy (IMRT) using tomotherapy accelerators (TA) in postoperative endometrial cancer (EC) regarding ICRU 83 recommendations. BACKGROUND: IMRT in gynecological malignancies provides excellent dosimetric data, lower rates of adverse events and clinical data similar to historical series. MATERIAL AND METHODS: Seventy-six patients with EC were postoperatively treated with adjuvant IMRT using TA. The IMRT dose was 45 Gy for patients without positive lymph nodes and Type I histology and 50.4 Gy for patients with positive lymph nodes and/or type II histology. RESULTS: With a median follow-up of 29 months, the 12- and 24-month Overall Survival (OS) and Disease-Free Survival (DFS) were 96%, 93%, 87%, and 74%, respectively. Age of less than 60 years was associated with better OS (HR: 8.9; CI: 1.1-68) and DFS (HR: 3.5; CI: 1.2-10.2). Patients with Type II and Type I Grade III histology had a worse OS (HR: 3.3; CI: 1.1-11). Five women (6.6%) presented in-field local vaginal recurrence, 2 (2.6%) presented non-in-field vaginal recurrence, 4 (5.2%) presented pelvic node and distant recurrence and 11 (14.4%) presented only distant metastases. One patient stopped radiation treatment due to Grade III acute diarrhea. No Grade III late toxicity was observed. Planning Target Volume (PTV) coverage showed mean D2, D50, D95, and D98 of 51.64-46.23 Gy, 49.49-44.97 Gy, 48.62-43.96 Gy, and 48.47-43.58 Gy for patients who received 45 and 50.4 Gy, respectively. CONCLUSIONS: IMRT with TA in postoperative EC shows excellent conformity and homogeneity of PTV dose. Without Grade III late toxicity, data from this cohort demonstrated the utility of IMRT.

What is the normal tissues morbidity following Helical Intensity Modulated Radiation Treatment for cervical cancer?

BACKGROUND AND PURPOSE: To report on normal tissues morbidity following IMRT for cervix cancer. MATERIAL AND METHODS: The first 61 patients of a prospective series were included. 50 Gy to the PTV 1(pelvis) and 60 Gy to the PTV 2 (centro-pelvic disease and GTV nodes) were delivered concomitantly in 28 fractions, followed by a brachytherapy boost. For the small bowel, 50 Gy was the maximal dose, while V45 and V40 had to be <50 cc and 200 cc, respectively. For the bladder, rectum and sigmoid structures, 60 Gy was the maximal dose, and V45 and V40 had to be <20% and <50%. Acute and late toxicity data were prospectively collected. RESULTS: The median follow-up period was 40 months (range: 23-60). 30% and 90% of acute and moderate late side effects were reported respectively. Considering the AUC data of the organs at risk (OAR) DVH, late morbidity and doses were significantly linked (p⩽0.03), predominantly between 10 Gy and 40 Gy, considering the small bowel and sigmoid colon. The high dose regions exhibited no significant impact. CONCLUSION: The moderate dose volumes represent the predominant cause of morbidity after IMRT. Prospective trials are thus required to investigate new ways of dose distribution within the OAR.

Concomitant Chemoradiotherapy With Image-guided Pulsed Dose Rate Brachytherapy as a Definitive Treatment Modality for Early-stage Cervical Cancer.

PURPOSE: Concurrent chemoradiotherapy (CRT) is the standard of care for patients with bulky cervical cancer. This study aimed to determine the feasibility, tolerance, and effectiveness of pulsed dose rate (PDR) image-guided brachytherapy (IGBT), utilizing magnetic resonance imaging (MRI) planning after CRT for stages IB2 and II cervix cancer patients. METHODS AND MATERIALS: This study planned to include patients with histologically confirmed stage IB2 and II cervical cancer who were treated with CRT followed by a PDR IGBT boost from January 2009 to December 2009 in our institution. All patients had at least a partial response after CRT before IGBT. The institutional review board approved the study. Patients received a 45-Gy external beam radiotherapy (EBRT) to the pelvis with concomitant weekly cisplatin (40 mg/m) for 5 cycles. All patients then underwent reimaging using MRI before BT. The IGBT boost was accomplished with one insertion using an MRI-compatible tandem and ovoid applicator delivering 30 to 35 Gy to a high-risk clinical target volume. Treatment-induced adverse events (AEs), dose parameters, local control, progression-free survival, and overall survival are reported. RESULTS: Forty patients were included in this study, with ages ranging from 31 to 65 years (median age, 45 y). Of all the patients, 12.5% and 5% experienced grade 3 to 4 acute gastrointestinal and genitourinary AEs, respectively, and 2.5% and 2.5% had grade 3 to 4 chronic gastrointestinal and genitourinary AEs, respectively. Within a median follow-up of 30 months (range, 7 to 40 mo), local control was 90%, progression-free survival was 87.5%, and overall survival was 100%. CONCLUSIONS: Intracavitary MRI PDR-IGBT boost after CRT is a feasible, tolerable, and effective treatment modality for patients with stages IB2 and II cervical cancer.

Feasibility study of pelvic helical IMRT for elderly patients with endometrial cancer.

PURPOSE: Standard treatment for early-stage endometrial cancer involves surgery (when possible) followed by brachytherapy or external-beam radiotherapy (EBRT) for high-risk tumors. EBRT is not without toxicity, meaning that it could be difficult to complete for elderly patients, who typically have decreased reserve and resistance to stressors. PATIENTS AND METHODS: Patients aged 70 and over treated between April 2009 and May 2013 for endometrial cancer and received IMRT (Intensity-Modulated Radiation Therapy) were included in this observational study. IMRT could be performed as adjuvant treatment or as an exclusive treatment for patients not amenable to surgery. The primary endpoints of this study were to assess the feasibility and toxicity of pelvic IMRT in this population. Secondary endpoints were to assess disease-specific survival, overall survival, and local control. Predictors of toxicity were also explored. RESULTS: Forty seven consecutive patients were included in the analysis. Median age at diagnosis was 75 years (range, 70-89 years). Eleven patients were aged 80 years and older. Toxicities were found in thirty four patients (72%) during treatment. Among these, toxicity did not exceed grade 2 for 32 patients (68%). Two patients had a grade 3 toxicity (4%). Overall survival rates were 87% and 83% at 1 and 2 years, respectively. Six patients (12.8%) had a local relapse and nine others (19.1%) had distant relapse. CONCLUSIONS: Pelvic helical IMRT for patients aged 70 and older is feasible with full standard radiation doses, showing that age greater than 70 should not be considered as a reason not to perform optimal treatment.

Impact of post operative intensity modulated radiotherapy on acute gastro-intestinal toxicity for patients with endometrial cancer: results of the phase II RTCMIENDOMETRE French multicentre trial.

PURPOSE/OBJECTIVE: Whole "conventional" pelvic irradiation (up to 45-50Gy) following hysterectomy is associated with a high rate of adverse gastro-intestinal (GI) adverse events, of which around 60% correspond to acute grade 2 toxicity. The phase II RTCMIENDOMETRE trial was designed to test the hypothesis that IMRT could reduce the incidence of grade 2 or more acute GI toxicity to less than 30% in patients irradiated post-operatively for an endometrial cancer. MATERIALS/METHODS: Patients with post-operative stage Ib G3, Ic or II endometrial carcinomas with no history of chronic inflammatory bowel disease were eligible. Guidelines for volume delineation and dose prescription were detailed in the protocol. The investigators were advised to use a web-based atlas developed for the RTOG 0418 study. The dose of the vaginal and nodal PTV was 45Gy in 25 fractions. To assess the ability of the participating centres to comply with the protocol guidelines, they were requested to complete a dummy run procedure before inclusion of their 1st patient. GI and genito-urinary (GU) toxicity were graded according to the CTCAE V 3.0 classification and were prospectively recorded every week during irradiation, as well as at time of brachytherapy insertions and during the follow-up visit at week 15 (W15). Special attention was given to note any changes to the grade of adverse events between W5 and W15. RESULTS: From May 2008 to April 2010, 49 patients from 6 centres were recruited for the trial. One patient could not be treated, one patient died of vascular stroke at W3 without toxicity, and 1 patient refused to be followed-up after treatment. Thus, 46 cases were available for analysis at W15. The distribution by stage was as follows: Ib 16.3%, Ic 64.2%, II 20.4%. Thirty six patients (75%) received an additional vaginal vault boost of 6-10Gy delivered by HDR brachytherapy in 1 or 2 fractions. Among the 47 patients who completed IMRT, 27% (95% CI 14.5-39.7%) developed at least 1 GI grade 2 adverse event (diarrhoea in 92% of cases), which mainly occurred at W4 and W5. No event corresponding to grade 3 or above was recorded. At W15, the number of patients complaining about GI events was low: 5 patients complained about persistent grade 1 diarrhoea, and 4 patients complained about haemorrhoids. Nineteen percent (95% CI 8.9-32.6%) of patients experienced grade 2 cystitis or urinary frequency which had disappeared by W15. CONCLUSION: In accordance with our hypothesis, post-operative IMRT resulted in a low rate (less than 30%) of acute GI grade 2 toxicity, in patients with endometrial carcinomas. At W15, no patient demonstrated a grade 2 adverse event, and the prevalence of remaining grade 1 events was less than 20%.

Volume-based pulsed-dose-rate brachytherapy boosting concurrent chemoradiation as a definitive treatment modality in cervical cancer.

PURPOSE: To report the treatment outcomes and treatment-induced adverse events (AEs) of concomitant chemoradiotherapy boosted with pulsed-dose-rate brachytherapy using volume-based two-dimensional planning in patients with cervical cancer. PATIENTS AND METHODS: After obtaining the institutional review board approval, patients with FIGO Stages IB to IIIB cervical cancer, treated from January 2006 to December 2008 consecutively, were included. Volume-based planning was used and entailed defining an envelope around the tumor on a two-dimensional image and prescribing the dose to this envelope and reporting the dose of the isodose of 60 Gy. Patients and tumor characteristics, dosimetric parameters, AEs and treatment outcomes, local control rate, distant metastases rate, progression-free survival, and overall survival are reported. RESULTS: The study included 95 patients; the median age is 50 years. The median tumor size is 50cc (range, 25-78cc). Median brachytherapy dose delivered to the envelope is 20 Gy (range, 15-35 Gy), and median volume encompassed by 60 Gy isodose curve is 137cc (range, 26-365cc). The 3-year overall survival, progression-free survival, local control rate, and distant metastases rate were 83.8%, 72.4%, 84.8%, and 15.4%, respectively. Gastrointestinal and genitourinary Grade 3 and 4 acute AEs were reported in 11.6% and 3.3% and chronic Grade 3 and 4 AEs were reported in 3.2% and 4.2% of all patients, respectively. CONCLUSIONS: Chemoradiotherapy followed by pulsed-dose-rate brachytherapy boost is effective and tolerable treatment modality for locally confined cervical cancer.

Laparoscopic radical hysterectomy after preoperative brachytherapy for stage IB1 cervical cancer: feasibility, results, and surgical implications in a large bicentric study of 162 consecutive cases.

PURPOSE: To examine the feasibility and to report the results of laparoscopic radical hysterectomy (LRH) after initial uterovaginal brachytherapy (BT) for stage IB1 cervical cancer. METHODS: We retrospectively reviewed patients at 2 comprehensive cancer centers who underwent initial BT followed 6-8 weeks later by LRH and lymph node dissection. RESULTS: Between 2003 and 2010, a total of 162 patients underwent LRH. The procedure was feasible via this approach in 160 cases (98.8%) (2 conversions to laparotomy). Eight perioperative complications occurred. Nineteen patients had nodal involvement. Peri- or postoperative ureteral morbidity occurred in 10 patients (6%). Twenty-four patients (15%) experienced postoperative dysuria. Histologically, only 9 patients had residual cervical disease ≥5 mm, and only 1 patient had parametrial lymphovascular space involvement (associated with nodal spread). No patient had vaginal disease or involved surgical margins. After a median follow-up of 39 (range 3-118) months, 9 patients experienced relapse. Five-year overall survival was 95% (range 88.2-97.9%). CONCLUSIONS: Radical hysterectomy using a laparoscopic approach is feasible and reproducible after initial BT for stage IB1 cervical cancer and is associated with excellent survival. Morbidity is close to that reported in patients treated with up-front surgery. In this large series, the morbidity associated with parametrial dissection and the fact that parametrial spread was observed in only 0.6% of the patients suggest that a simple extrafascial hysterectomy is perhaps sufficient in this context; the rate of urinary tract morbidity would then be reduced.

Benefit of robot-assisted laparoscopy in nerve-sparing radical hysterectomy: urinary morbidity in early cervical cancer.

OBJECTIVE: To evaluate the feasibility of nerve-sparing radical hysterectomy in early cervical cancer by robot-assisted laparoscopy and atonic bladder rate. METHODS: This was a retrospective study with consecutive patients in three gynecological oncology departments. Patients with <2 cm cervical cancer had nerve-sparing radical hysterectomy by robot-assisted laparoscopy and pelvic lymphadenectomy. Two days after surgery, we systematically removed the Foley bladder catheter. RESULTS: The median (range) age and body mass index of the 30 patients were 44 (33-68) years and 23.9 (17.7-39.4) kg/m(2), respectively. The median (range) tumor diameter at the time of surgery was 13 (4-38) mm. The median (range) operative time, blood loss, and number of pelvic lymph nodes (any common iliac lymph nodes) were 305 (180-405) min, 100 (30-1,500) ml, and 18 (7-28). The overall complication rate was 52.3 %, of which 6.7 % atonic bladder. Twenty-eight patients (93.3 %) were discharged 2 days after surgery with spontaneous voiding and no residual urine >100 ml. CONCLUSIONS: Nerve-sparing radical hysterectomy by robot-assisted laparoscopy is feasible in early cervical cancer (<2 cm). A total of 93.3 % of the patients were discharged 2 days after surgery with spontaneous voiding. The next step would be a prospective study with objective urodynamic investigations.

[Radiation therapy versus chemoradiation as adjuvant treatment in high-risk endometrial cancer]. / Radiothérapie versus radiochimiothérapie comme adjuvant à la chirurgie dans les cancers de l'endomètre à haut risque.

Endometrial cancer is a common malignancy. Management of these tumors depends on several risk factors such as FIGO staging, myometrial invasion, histology or pelvic lymph node involvement. According to those factors, low risk, intermediate and high risk groups were defined. A high risk endometrial cancer has a poorer prognostic and more risks of recurrence. Treatment of such disease should be more aggressive. However modalities of these treatments have not yet been clearly defined.