Optimizing Local Control in High-Grade Uterine Sarcoma: Adjuvant Vaginal Vault Brachytherapy as Part of a Multimodal Treatment.

PURPOSE: The phase III European Organization for Research and Treatment of Cancer 55874 study has shown that external beam radiotherapy (EBRT) given as adjuvant treatment decreased locoregional recurrences from 40% to 20% in patients (pts) with localized uterine sarcomas (US). No data exist, however, on the place of brachytherapy (BT). MATERIAL AND METHODS: We conducted a single-center retrospective analysis of pts receiving adjuvant BT of the vaginal vault based on the vaginal mold technique as part of their multimodal adjuvant treatment for a high-grade US from 1985 to 2015. Treatment characteristics, patterns of relapse, and toxicity were examined. RESULTS: Median follow-up time was 5.5 years. A total of 98 pts with high-grade US were identified: 81 leiomyosarcomas and 17 undifferentiated sarcomas. Postoperative chemotherapy was delivered in 53 pts. Median dose of EBRT was 45 Gy in 25 fractions. High-dose rate, low-dose rate, and pulsed-dose rate techniques were used in 66, 31, and 1 pts, respectively. At last follow-up, six pts (6.1%) experienced a locoregional relapse as first event. The International Federation of Gynecology and Obstetrics stage and the tumor size were associated with a higher probability of local relapse. When focusing on pts with stage I-III disease, 5-year overall survival was 77% (95% confidence interval: 67%-87%) and 5-year survival without locoregional failure was 91% (83%-98%). Toxicities were mild to moderate, with only four acute grade 3 toxicities and two grade 3 late effects. CONCLUSION: Vaginal vault BT as part of a multimodal adjuvant treatment was associated with a high locoregional control rate and with acceptable side effects in localized high-grade US. The Oncologist 2017;22:182-188Implications for Practice: This study suggests that an aggressive adjuvant treatment combining chemotherapy and pelvic external beam radiotherapy followed with a brachytherapy of the vaginal vault is associated with a high locoregional control rate and an acceptable toxicity rate in patients with high grade uterine sarcoma. Adding a brachytherapy boost could also allow deescalating the total dose of pelvic external beam radiotherapy, in order to decrease the side effects of adjuvant treatment in these patients without increasing the risk of local relapse. However, the prognosis remains determined by a high frequency of systemic relapses.

Chemotherapy Regimen in Nonagenarian Cancer Patients: A Bi-Institutional Experience.

BACKGROUND: The elderly population in Western countries is growing and constitutes a public health issue. Concomitantly, age-related diseases such as cancer increase. There are few data on the efficacy, tolerability and toxicity of specific anticancer therapy in the very elderly patients; therefore, their management is not standardized. METHODS: In this bi-institutional study, we reviewed medical records of patients who received or continued specific anticancer therapy beyond the age of 90 years. Geriatric assessment was not reported for our patients. Twelve patients were enrolled. Their general health condition was good, and half of them were living in elderly institutions. Ten patients had a solid tumor and 2 were treated for hematological malignancies. Most were diagnosed with a locally advanced or metastatic disease, and the goal of treatment was curative for only 1 patient. Six patients received chemotherapy as first-line treatment, 4 patients received targeted therapy and 2 received concomitant chemoradiation. Four patients received a second-line treatment. RESULTS: Despite a significant reduction in treatment posology in half of the patients, 8 acute grade 3/4 toxicities were reported and 2 patients died of treatment-related septic shock. Median duration of first-line treatment was 3.2 months, and progression-free survival ranged from 18 to 311 days. Overall survival ranged from 18 days to 11 years. CONCLUSION: Aging is a heterogeneous process, and management of elderly patients is a multidisciplinary approach. Geriatric assessment helps to identify older patients with a higher risk of morbidity/mortality and allows to assess the risks and benefits of specific anticancer therapy. The choice of treatment should be based primarily on the expected symptomatic benefit, and treatment should not compromise the quality of life.

Safety of spinal radiotherapy in metastatic cancer patients receiving bevacizumab therapy: a bi-institutional case series.

We retrospectively assessed the outcome of patients receiving emergency spinal radiation therapy (RT) concurrently with bevacizumab. Clinical records of 18 consecutive patients receiving emergency spinal RT for symptomatic vertebral metastases during the course of bevacizumab-based therapy were examined. Patients were receiving biweekly bevacizumab combined with paclitaxel (n=17) or with docetaxel/carboplatin (n=1) or as a single agent (n=1) for advanced metastatic carcinoma. RT was delivered at doses of 30 Gy in 10 fractions (n=8), 20 Gy in five fractions (n=9) or 18 Gy in nine fractions (n=1). In 10 patients (56%), irradiation field encompassed the thoracic vertebrae. The median time interval between the bevacizumab infusion and the RT course was 1.5 days (0-8 days). The median follow-up was 8.3 months (2 days-42 months). A clinical benefit of RT was reported in 13 patients (72%), including four patients with complete pain relief. Two of the three patients with neurological impairment at the time of RT experienced a partial improvement in their symptoms. No pain recrudescence was reported within the irradiated field after RT completion. All toxicities were mild to moderate, with no acute toxicity reported in 13 patients (72%). No RT disruption was necessary because of acute toxicity. No delayed toxicity was reported within RT fields among 11 patients with at least 6 months of follow-up. Spinal RT during the course of bevacizumab-based therapy was not associated with the occurrence of unexpected adverse effects. This suggests that emergency RT should not be contraindicated in these patients, provided that doses and treatment volumes are defined carefully.

Radiotherapy for head and neck cancer in nonagenarian patients: a possible cornerstone?

In the field of radiotherapy, there is very little scientific data on the management of nonagenarians, especially in patients aged 90 years or more and with head and neck cancer (HNC). We made one of the first retrospective study of the feasibility and safety of radiotherapy in this population with HNC. Records of radiotherapy coming from four health facilities were studied to include all nonagenarian patients with HNC in the last 10 years and who received radiation therapy. We analyzed patient characteristics and primary cancers, as well as objective of the treatment (curative or palliative), efficacy and toxicity. Twenty patients receiving radiotherapy were identified; mean age was 93.2 years (standard deviation 2.8). Treatment was given with curative and palliative intent in 40 and 60 % of cases, respectively. The most common primary tumors were tumors of the salivary glands (30 % of cases), oral cavity tumors (25 % of cases) and thyroid tumors (15 % of cases). Median total prescribed dose was 47.5 Gy (12-70 Gy). Median number of delivered fractions was 18.5 (2-35 fractions). All patients received intensive supportive care during radiotherapy. Toxicities were mild to moderate. Radiotherapy could not be completed for four patients (20 % of cases). One patient developed grade 1-2 delayed toxicities. At the last follow-up, only four patients (20 % of cases) were alive. Cancer was cause of death in most cases. Radiotherapy may be performed for the nonagenarians with HNC. The total dose and fractionation must be adjusted to optimize the tolerance. However, the prognosis remains very poor, cancer being the main cause of death. Research of geriatric vulnerabilities prior to any treatment, in the context of a comprehensive geriatric assessment, is still recommended to select patients for radiotherapy.

Redefining the role of pulsed-dose-rate brachytherapy in cervical cancer treatment using a preplanned approach.

INTRODUCTION: This study aims to determine predictive factors for cervical cancer patients who would benefit more from high-dose-rate (HDR) or pulsed-dose-rate (PDR) brachytherapy. METHODS: The sample included 50 patients treated with brachytherapy following external radiochemotherapy. PDR plans were compared to HDR preplans, with a focus on patients who may benefit from PDR using preplan metrics and clinical variables. The expected clinical effect was quantified using a tumor control probability model. RESULTS: Results showed PDR plans with 60 pulses to be optimal for achieving target clinical goals for D90CTVHR. A CTVHR volume of >67.5cc and/or D90CTVHR dose on the HDR preplan of <31.1 Gy was the strongest indicator for patient selection who would gain >3% increase in TCP with PDR. The process showed 96% accuracy, 88% sensitivity, and 98% specificity. Only 16% of patients showed a relevant benefit from PDR over HDR, with a mean D90CTVHR of 7 Gy higher and a mean TCP at 3 years of 4.8% higher for PDR. The benefit of PDR is highly influenced by the choice of alpha/beta ratio and repair halftime. CONCLUSION: A small subset of cervical cancer patients may gain from PDR over HDR. CTVHR volume and preplan D90CTVHR doses may be useful in selecting patients for PDR brachytherapy.

Brachytherapy boost in anal canal cancer - A GEC ESTRO PDR task force meta-analysis.

Purpose: A meta-analysis is presented comparing clinical outcomes and toxicities between high dose rate (HDR) and pulsed dose rate (PDR) brachytherapy (BT) for anal cancer. Methods and material: Retrospective or prospective clinical trials were identified on electronical databases. Data were collected per Preferred Reporting Items for Systematic Reviews and meta-Analyses guidelines. Pooled effect size for HDR and PDR BT were compared using subgroup analyses. Results: Nine retrospective studies with a total of 481 patients treated were included of which 219 with HDR and 262 with PDR. Significant differences were observed between the two groups for baseline characteristics and treatment. The cumulative proportion of stage T3-T4 was lower in the HDR group, 0.15 [95 % confidence interval (CI) 0.07-0.29] vs 0.27 [95 %CI 0.09-0.57] in the LDR group, p < 0.001. Lower BT doses (in equivalent 2-Gy fraction dose) were given for patients in the HDR group, 11.9 Gy [95 %CI 8.2-15.5] vs 19.5 Gy [95 %CI 15.0-24.0] in the PDR group, p < 0.001. No significant differences were found for clinical outcomes or toxicities. The pooled effect size of the overall survival at 5 years for HDR and PDR was respectively 0.82 [95 %CI 0.70-0.94] and 0.82 [95 %CI 0.73-0.91], p > 0.99. The 5 years local control was 0.86 [95 % confidence interval (CI) 0.81-0.91] and 0.83 [95 %CI 0.77-0.89], p = 0.62. Cumulative toxicity-related colostomy proportion was 0.04 [95 %CI 0.02-0.09] and 0.03 [95 %CI 0.02-0.07], p = 0.85. Conclusion: Both modalities provided a good profile of tolerance and are effective organ conservative strategies for patients with anal canal cancer. In parallel with ongoing developments to better determine the optimal fractionation and dose for HDR-BT treatments, especially in large tumors, PDR BT still has a crucial role for dose escalation strategy in advanced cases.

A novel lung SBRT treatment planning: Inverse VMAT plan with leaf motion limitation to ensure the irradiation reproducibility of a moving target.

This study exposed the implementation of a novel technique (VMATLSL) for the planning of moving targets in lung stereotactic body radiation therapy (SBRT). This new technique has been compared to static conformal radiotherapy (3D-CRT), volumetric-modulated arc therapy (VMAT) and dynamic conformal arc (DCA). The rationale of this study was to lower geometric complexity (54.9% lower than full VMAT) and hence ensure the reproducibility of the treatment delivery by reducing the risk for interplay errors induced by respiratory motion. Dosimetry metrics were studied with a cohort of 30 patients. Our results showed that leaf speed limitation provided conformal number (CN) close to the VMAT (median CN of VMATLSL is 0.78 vs 0.82 for full VMAT) and were a significant improvement on 3D-CRT and DCA with segment-weight optimized (respectively 0.55 and 0.57). This novel technique is an alternative to VMAT or DCA for lung SBRT treatments, combining independence from the patient's breathing pattern, from the size and amplitude of the lesion, free from interplay effect and with dosimetry metrics close to the best that could be achieve with full VMAT.

Repeated Multimodality Ablative Therapies for Oligorecurrent Pulmonary Metastatic Disease.

Stereotactic body radiotherapy (SBRT) and percutaneous thermal ablation (TA) are alternatives to surgery for the management of pulmonary oligometastases. In this collaborative work, we retrospectively analyzed patients who had undergone iterative focal ablative treatments of pulmonary oligometastases. We hypothesized that repeated ablative therapies could benefit patients with consecutive oligometastatic relapses. Patients treated with SBRT and/or TA for pulmonary oligometastases in two French academic centers between October 2011 and November 2016 were included. A total of 102 patients with 198 lesions were included; 45 patients (44.1%) received repeated focal treatments at the pulmonary site for an oligorecurrent disease (the "multiple courses" group). Median follow-up was 22.5 months. The 3-year overall survival rates of patients who had a single treatment sequence (the "single course" group) versus the "multiple courses" were 73.9% and 78.8%, respectively, which was not a statistically significant difference (p = 0.860). The 3-year systemic therapy-free survival tended to be longer in the "multiple courses" group (50.4%) than in the "single course" group (44.7%) (p = 0.081). Tolerance of repeated treatments was excellent with only one grade 4 toxicity. Thereby, multimodality repeated ablative therapy is effective in patients with pulmonary oligorecurrent metastases. This strategy may delay the use of more toxic systemic therapy.

Reducing dose to rectum by placement of a rectum-emptying tube in cervical cancer patients treated with brachytherapy.

PURPOSE: Only scarce data are available on the possibility to reduce rectal dose by controlling rectum filling before HDR (high dose rate) IGABT (image-guided adaptive brachytherapy) in LACC (locally advanced cervical carcinoma) patients. We compared dosimetric outcomes before and after the evacuation of gasses using a rectum emptying tube. METHODS AND MATERIAL: Sixty CT (computed tomography) scans from 30 consecutive patients with cancer of the cervix undergoing HDR IGABT after EBRT were reviewed. Patients who underwent at least one gas evacuation were included in the analysis. The three-dimensional dosimetric data of the dosimetric plan performed before and after gas evacuation were compared. Primary endpoint was the difference between D2cc of the rectum before and after the procedure. Expected probability of grade 2-4 overall rectum morbidity was assessed using a probit model from the prospective multicenter EMBRACE study. RESULTS: Thirty five (58.3%) CT scans from 23 patients (76.7%) requiring gas evacuation were analysed. The mean rectum volume, before and after gas evacuation, was 123.1 cc (sd, ± 60.4) and 66.4 cc (sd, ± 34.8), respectively. For each patient, the volume of the rectum after gas evacuation was lower than before. No major complication occurred during and after the procedure. After gas evacuation, a significant reduction in rectal dose per fraction was observed, on average -4.3 Gy (-38.4%, p < 0.001) for D0.1cc and -1.9 Gy (-30.6%, p < 0.001) for D2cc. Estimated mean probability to develop a grade 2-4 rectum morbidity was significantly lower after gas evacuation, 6.9% (sd,± 1.94) versus 9.5% (sd,± 3.17), p < 0.001. CONCLUSION: Gas evacuation using a rectal emptying tube in selected LACC patients treated with HDR BT after chemoradiotherapy, allowed a substantial reduction in the dose to the rectum. Such procedure could be of particular interest when a dose escalation strategy is being considered.

[Start of activity with the MRIdian® system: The first 200 patients treated at the Institut Paoli-Calmettes]. / Retour d'expérience clinique à propos des 200 premiers patients traités au MRIdian® à l'Institut Paoli-Calmettes.

INTRODUCTION: Several centers have recently been equipped with MRI-guided radiotherapy systems, including the Paoli-Calmettes Institute which was the first French center to start this activity. We report in this article our early experience. METHODS: Data related to patients treated on the MRIdian® (Viewray®) were prospectively collected. Procedures concerning the implementation of the system and internal organizational issues were summarized. RESULTS: Between February 2019 and March 2020, 201 patients were treated: 40% of treatments were normofractionated (n=70) and 60% used hypofractionation (n=105). The reported monthly occupancy rate at one, six and twelve months was 30%, 62%, and 90%. The distribution of normofractionated treatments was dominated by prostatic (29%) and pancreatic (26%) cancers, followed by abdomino-pelvic irradiations for gynecological cancers (12%) or lymph node diseases (12%) and boosts for rectal or vaginal cancers (11%). Regarding treatments with moderate hypofractionation (dose by fraction between 3 and 5Gy), they corresponded mainly to integrated boost for abdomino-pelvic lymph nodes (38%), while the stereotaxic treatments primarily concerned hepatic lesions (15%), bones (30%). DISCUSSION: The MRIdian® was initially used widely in our service corresponding to a learning curve for MRI guidance. This new tool for image-guided radiotherapy helped us to secure our practice providing solutions for both inter and intra-fraction movements making it possible to reduce the additional margin in order to better protect the organs at risk. The main technical difference with conventional accelerators is the possibility of performing adaptive radiotherapy in real time, the start of which was more gradual.

Radiobiology: Foundation and New Insights in Modeling Brachytherapy Effects.

Fundamentals in radiobiology commonly known as the '4R's' concept (ie, reoxygenation, repair, redistribution, and repopulation) have mostly been investigated for external beam radiotherapy. However, these fundamentals can be applied to brachytherapy (BT) by accounting for differences in dose rate, fractionation, and response to immunologic agents for this treatment modality. Many improvements have been achieved in the era of dosimetric optimization but still limited data are available regarding radiobiological opportunities for BT. As BT is characterized by a large degree of dose heterogeneity, a wide range of dose rates and fractionations exist within the implanted volume. Calculations based on the linear quadratic model can be used to estimate the dose-response equivalence between various BT modalities. Such models are helpful in daily practice and open possibilities in terms of radiobiological optimization. However, some limitations should be highlighted in terms of the applicability of the linear quadratic model. Furthermore, in vitro models do not account for the complex interplay between the tumor and its microenvironment, including vascularization and/or immune response. Recently, an improved understanding of the tumor's microenvironment has led to investigations of immunomodulatory agents in combination with radiotherapy. BT is a promising candidate to enhance the immunogenic response with concomitant immunotherapy. This review summarizes some of the main mechanisms involved in tissue response to BT. Preclinical data, clinical evidence, as well as novel approaches to radiobiology are highlighted.

Incorporating Magnetic Resonance Imaging (MRI) Based Radiation Therapy Response Prediction into Clinical Practice for Locally Advanced Cervical Cancer Patients.

In recent years, magnetic resonance imaging (MRI) has become one of the standard imaging tools to define the macroscopic gross tumor volume in locally advanced cervical cancer patients based on T2-weighted sequence. Recent data suggest that functional MRI could be used to potentially improve the delineation of target volumes based on physiologic features, defining radioresistant subvolumes that may require higher doses to achieve local cure. Functional imaging can be used to predict tumor biology and outcome, as well as for assessment of tumor response during radiotherapy. The concept of adaptive radiotherapy relies on the possibility of monitoring variations in target volumes structures to guide treatment-plan modification during radiotherapy, taking into account not only internal movements but also tumor response. With integrated MRI in radiotherapy linear accelerators, motion monitoring during treatment delivery has become available. MRI can be also used to accurately evaluate cervical tumor residual volume after chemoradiotherapy, and therefore allowing a personalized treatment planning for brachytherapy boost, based on tumor radiosensitivity. In this review, we discuss how MRI tumor response assessment could be included into clinical practice during radiation therapy in locally advanced cervical cancer patients.

Esophageal brachytherapy: Institut Gustave Roussy's experience.

PURPOSE: Esophageal cancer is characterized by its propension to local evolution, which conditions prognosis and quality of life. Brachytherapy may be a therapeutic option for all stages of esophageal cancer. METHODS AND MATERIALS: This retrospective unicentric study included all consecutive patients treated for an esophageal high-dose-rate brachytherapy in our institution from 1992 to 2018. RESULTS: Ninety patients were included. They were treated in four distinct indications: exclusive (7 patients), boost after external beam radiotherapy (41), reirradiation (36), or palliative aim (6). Most frequently prescribed schemes were 3 × 5 Gy (boost) or 6 × 5 Gy (exclusive treatment and reirradiation) at applicator's surface or at 5 mm. At the end of follow-up, 50% of patients had presented with local recurrence. Seventeen percent of patients had a metastatic relapse. Median overall survival was 15 months in the whole cohort: 22 months in the boost setting, 25 months for exclusive brachytherapy, 15 months for reirradiation, and only 2 months for palliative treatment. Tumor length at brachytherapy, brachytherapy dose, and interfraction response were significantly associated to overall survival. 40% of patients presented with grade 2+ toxicity, mostly esophagitis, including three toxic deaths. CONCLUSIONS: Although local control outcomes are still poor, one must remember that patients are unfit for any curative therapeutic option and that palliative chemotherapy offers mediocre results. The most promising setting probably is reirradiation because brachytherapy offers a remarkable dose gradient allowing best organ at risk sparing, with an encouraging rate of long survivors (19% at 2 years). Esophageal brachytherapy deserves to be further investigated because some patients, even unfit, may benefit from it, with acceptable toxicity.

Radiobiological optimization comparison between pulse-dose-rate and high-dose-rate brachytherapy in patients with locally advanced cervical cancer.

PURPOSE: Only scarce data are available on the possibility to include radiobiological optimization as part of the dosimetric process in cervical cancer treated with brachytherapy (BT). We compared dosimetric outcomes of pulse-dose-rate (PDR) and high-dose-rate (HDR)-BT, according to linear-quadratic model. METHODS AND MATERIALS: Three-dimensional dosimetric data of 10 consecutive patients with cervical cancer undergoing intracavitary image-guided adaptive PDR-BT after external beam radiation therapy were examined. A new HDR plan was generated for each patient using the same method as for the PDR plan. The procedure was intended to achieve the same D90 high-risk clinical target volume with HDR as with PDR planning after conversion into dose equivalent per 2 Gy fractions (EQD2) following linear-quadratic model. Plans were compared for dosimetric variables. RESULTS: As per study's methodology, the D90 high-risk clinical target volume was strictly identical between PDR and HDR plans: 91.0 Gy (interquartile: 86.0-94.6 Gy). The median D98 intermediate-risk clinical target volume was 62.9 GyEQD2 with HDR vs. 65.0 GyEQD2 with PDR (p < 0.001). The median bladder D2cc was 65.6 GyEQD2 with HDR, vs. 62 GyEQD2 with PDR (p = 0.004). Doses to the rectum, sigmoid, and small bowel were higher with HDR plans with a median D2cc of 55.6 GyEQD2 (vs. 55.1 GyEQD2, p = 0.027), 67.2 GyEQD2 (vs. S 64.7 GyEQD2, p = 0.002), and 69.4 GyEQD2 (vs. 66.8 GyEQD2, p = 0.014), respectively. For organs at risk (OARs), the effect of radiobiological weighting depended on the dose delivered. When OARs BT contribution to D2cc doses was <20 GyEQD2, both BT modalities were equivalent. OARs EQD2 doses were all higher with HDR when BT contribution to D2cc was ≥20 GyEQD2. CONCLUSION: Both BT modalities provided satisfactory target volume coverage with a slightly higher value with the HDR technique for OARs D2cc while intermediate-risk clinical target volume received higher dose in the PDR plan. The radiobiological benefit of PDR over HDR was predominant when BT contribution dose to OARs was >20 Gy.

Quality of Life During Chemotherapy for Breast Cancer in a West African Population in Dakar, Senegal: A Prospective Study.

PURPOSE: The prevalence of breast cancer is increasing in low- to middle-income countries such as Senegal. Our prospective study assessed the quality of life (QoL) of patients with breast cancer undergoing chemotherapy in Senegal. PATIENTS AND METHODS: Our study included women with breast cancer undergoing chemotherapy as initial treatment at the Center Aristide Le Dantec University Hospital in Dakar. Clinical, sociodemographic, and QoL data were collected and analyzed at three different times: baseline, 3 months, and 6 months after the start of systemic therapy. Health-related QoL was assessed using a Functional Assessment of Cancer Therapies-Breast (FACT-B) questionnaire after translation into the Wolof language. Linear mixed-effects models were performed to assess the changes in QoL scores. RESULTS: Between July 2017 and February 2018, 120 patients were included in the study. Their median age was 45 years. Most patients (n = 105; 92%) had locally advanced disease (T3 to T4 stage) and lymph node involvement (n = 103; 88%), and half had metastatic disease. The FACT-B total scores significantly improved over time (ß = 1.58; 95% CI, 0.50 to 2.67; P < .01). Nausea and vomiting were significantly associated with a decrease in FACT-B total scores (ß = -16.89, 95% CI, -29.58 to -4.24, P = .012; and ß = -13.44, 95% CI, -25.15 to -1.72, P = .028, respectively). CONCLUSION: Our study confirmed the feasibility of standardized QoL assessment in Senegalese patients with breast cancer. Our results indicated a potential improvement of QoL over the course of chemotherapy. Optimizing nausea and vomiting prevention may improve QoL.

Multivariate normal tissue complication probability modeling of vaginal late toxicity after brachytherapy for cervical cancer.

PURPOSE: To explore the best variables combination for a predictive model of vaginal toxicity in cervical cancer patients undergoing brachytherapy (BT). METHODS AND MATERIALS: Clinical and 3-dimensional dosimetric parameters were retrospectively extracted from an institutional database of consecutive patients undergoing intracavitary BT after external beam radiation therapy from 2006 to 2013 for a cervical cancer. A least absolute shrinkage and selection operator selection procedure in Cox's proportional hazards regression model was performed to select a set of relevant predictors for a multivariate normal tissue complication probability model of Grade ≥2 vaginal late toxicity. Outcomes reliability was internally assessed by bootstrap resampling method. RESULTS: One hundred sixty-nine women were included in the present study with a median followup time of 3.8 years (interquartile range [IQR], 1.9-5.6 years). The 2 years and 5 years cumulative incidence rates of Grade ≥2 late vaginal toxicity were 19.9% and 27.5%, respectively. Among 31 metrics and six clinical factors extracted, the optimal model included two dosimetric variables: V70Gy and D5% (the percentage volume that received a dose greater or equal to 70 Gy and the minimum dose given to the hottest 5% volume, respectively). Area under the ROC curve at 2 and 5 years of followup were 0.85 and 0.91, respectively. Regarding internal validation, median area under the ROC curve of bootstrap predictions was 0.83 (IQR, 0.78-0.88) and 0.89 (IQR, 0.85-0.93) at 2 and 5 years of followup, respectively. CONCLUSIONS: A multivariate normal tissue complication probability model for severe vaginal toxicity based on two dosimetric variables (V70Gy and D5%) provides reliable discrimination capability in a cohort of cervical cancer treated with external beam radiation therapy and BT.

Tumor Shrinkage During Chemoradiation in Locally Advanced Cervical Cancer Patients: Prognostic Significance, and Impact for Image-Guided Adaptive Brachytherapy.

PURPOSE: To study the prognostic value of gross tumor volume (GTV) shrinkage and its dosimetric implication in a large cohort of patients with cervical cancer receiving definitive chemoradiotherapy plus image guided adaptive brachytherapy. METHODS AND MATERIALS: Clinical records of consecutive patients treated in our institution between February 2004 and November 2015 by concurrent chemoradiotherapy (45 Gy in 25 fractions ± lymph node boosts) followed by a magnetic resonance imaging-guided adaptive pulse-dose rate brachytherapy were included. The prognostic value of GTV and its evolution after chemoradiotherapy were examined first on initial staging magnetic resonance imaging and then at time of brachytherapy. All measures and measurement cutoffs were selected using time-dependent area under the curve for 3-year progression-free survival (PFS). RESULTS: GTV evolution between diagnosis and the time of brachytherapy was assessed in 247 patients. After chemoradiotherapy, complete response was observed in 75 patients (28%). Optimal cutoffs were GTV = 55 cm3 at diagnosis, GTV = 7.5 cm3 at brachytherapy, and GTV reduction ≥90%. All patients with volume above or reduction below these cutoffs had significant reduced overall survival, PFS, local control, and distant metastasis control (P < .001). Patients with anemia at diagnosis had a lower tumor volume response rate (P < .001). In multivariate analysis, incorporating the International Federation of Gynecology and Obstetrics stage, N+ stage, anemia, and dosimetric parameters for image guided adaptive brachytherapy, GTV optimal volume reduction after chemoradiotherapy was independently associated with improved overall survival, PFS, local control, and distant metastasis control (P < .001). CONCLUSIONS: These results could provide a rationale for dose de-escalation studies in brachytherapy for patients displaying optimal GTV volumetric reduction after chemoradiotherapy and may reinforce the need for dose escalation in poorly responding patients.

Radiation induced gastroparesis-case report and literature review.

Radiation induced gastroparesis as well as the other autonomic nervous system radiation induced neuropathies are poorly described in the literature. A case of gastroparesis associated with phrenic and recurrent laryngeal nerves paralysis was observed in a 69-year old patient. She was already treated two times by rachis radiotherapy in a context of breast cancer with bone metastases. Anatomical and chronological correlation of lesions, concomitant nerve damage in the radiation fields and elimination of the main differential diagnoses allowed us to link this case of gastroparesis with the background of radiotherapy. It confirms the role of vagus nerve lesion in radiation induced gastroparesis. This specific diagnosis led to a successful treatment and a quality of life improvement.

Inflammatory bowel diseases activity in patients undergoing pelvic radiation therapy.

BACKGROUND: Few studies with contradictory results have been published on the safety of pelvic radiation therapy (RT) in patients with inflammatory bowel disease (IBD). METHODS: From 1989 to 2015, a single center retrospective analysis was performed including all IBD patients who received pelvic external beam radiation therapy (EBRT) or brachytherapy (BT) for a pelvic malignancy. Treatment characteristics, IBD activity and gastrointestinal (GI) toxicity were examined. RESULTS: Overall, 28 patients with Crohn's disease (CD) (n=13) or ulcerative colitis (n=15) were included in the present study. Median follow-up time after irradiation was 5.9 years. Regarding IBD activity, only one and two patients experienced a severe episode within and after 6 months of follow-up, respectively. Grade 3/4 acute GI toxicity occurred in 3 (11%) patients, whereas one (3.6%) patient experienced late grade 3/4 GI toxicity. Only patients with rectal IBD location (P=0.016) or low body mass index (BMI) (P=0.012) experienced more severe IBD activity within or after 6 months following RT, respectively. CONCLUSIONS: We report an acceptable tolerance of RT in IBD patients with pelvic malignancies. Specifically, a low risk of uncontrolled flare-up was observed.

Flattening Filter Free vs. Flattened Beams for Lung Stereotactic Body Radiation Therapy.

BACKGROUND/AIM: To assess the clinical impact of high dose rate stereotactic body radiation therapy (SBRT) in patients with lung neoplastic lesions. PATIENTS AND METHODS: From January 2014 to June 2016, a single-center retrospective analysis was performed including all patients treated by either flattening filter free (FFF) beams or flattening filter beams (FF) three-dimensional (3D) SBRT for lung neoplastic lesions. RESULTS: A total of 99 SBRT were performed on 75 patients. Among these, 29 SBRT were performed using a FFF technique while 70 other SBRT were done using a FF technique. Median follow-up time was 12.9 months. Overall, no difference between the two groups was found except for the mean beam on time which was reduced by 3.3 to 0.9 minutes in the FFF group (p<0.001). CONCLUSION: We report a low toxicity rate and a shortened beam on time in patients treated with 3D FFF SBRT for lung neoplastic lesions.