Cervical Cancer Associated with Pregnancy: Current Challenges and Future Strategies.

Cancer during pregnancy is defined as a tumor diagnosed in a pregnant woman or up to 1-year post-partum. While being a rare disease, cervical cancer is probably one of the most challenging medical conditions, with the dual stake of treating the cancer without compromising its chances for cure, while preserving the pregnancy and the health of the fetus and child. To date, guidelines for gynecological cancers are provided through international consensus meetings with expert panels, giving insights on both diagnosis, treatment, and obstetrical care. However, these expert guidelines do not discuss the various approaches than can be found within the literature, such as alternative staging modalities or innovative surgical approaches. Also, the obstetrical care of women diagnosed with cervical cancer during pregnancy requires specific considerations that are not provided within our current standard of care. This systematic review aims to fill the gap on current issues with regards to the management of cervical cancer during pregnancy and provide future directions within this evolving landscape.

Variability of treatment of locally advanced cervical cancer: How French multidisciplinary teams follow European guidelines?

INTRODUCTION: Cervical cancer is a global public health concern. Despite ESGO recommendations and FIGO classification changes, management of locally advanced cervical cancer (LACC) remains debated in France. Our study aimed to review LACC treatment practices and assess adherence to ESGO recommendations among different practitioners. METHODS: From February 2021 to August 2022, we conducted a survey among gynecologic oncology surgeons, radiation oncologists, and medical oncologists practicing in France and managing LACC (FIGO stages IB3-IVA) according to the 2018 FIGO classification. We analyzed responses against the 2018 ESGO recommendations as a "gold standard." RESULTS: Among 115 respondents (56% radiation oncologists, 30% surgeons, 13% medical oncologists), 48.6% of gynecologic surgeons didn't perform para-aortic lymphadenectomy (PAL) with significant radiologic pelvic involvement. PAL, when indicated by PET-CT, was more common in university hospitals (66.7% of surgeons). Surgeons in university hospitals also followed ESGO recommendations more closely. Overall, compliance with all ESGO recommendations was low: 5.7% of surgeons, 21.5% of radiation oncologists, and 60% of medical oncologists. Prophylactic para-aortic irradiation, per ESGO, was more frequent in comprehensive cancer centers (52% of radiation oncologists). CONCLUSION: Adherence to ESGO recommendations for LACC treatment appears low in France, particularly in surgery, with limited PAL in cases of lymph node negativity on PET-CT. However, these recommendations are more often followed by surgeons in university hospitals and radiation oncologists in cancer centers. Adherence to these recommendations may impact patient survival and warrants evaluation of care quality, justifying the organization of LACC management in expert centers.

Tolerance of Concurrent Adjuvant Radiation Therapy and Pembrolizumab for Triple Negative Breast Cancer: Real Life Experience.

Purpose: The current standard-of-care management of locally advanced triple negative breast cancer (TNBC) is based on neoadjuvant chemo-immunotherapy with pembrolizumab, surgery, radiation therapy (RT), and adjuvant pembrolizumab. However, the safety of combining pembrolizumab with adjuvant breast RT has never been evaluated. This study evaluated the tolerance profile of concurrent pembrolizumab with adjuvant RT in patients with locally advanced TNBC. Methods and Materials: This bicentric ambispective study included all the patients with early and locally advanced TNBC who received neoadjuvant chemo-immunotherapy with pembrolizumab and adjuvant RT as part of their treatment. The tolerance profile of adjuvant RT was evaluated and compared in patients who received concurrent pembrolizumab and in patients for whom pembrolizumab was withheld. Results: Fifty-five patients were included between July 2021 and March 2023. Twenty-eight patients received adjuvant RT with concurrent pembrolizumab (RT+P group), and 27 patients had pembrolizumab withheld while receiving adjuvant RT (RT-only group). Two patients developed grade ≥3 toxicity (1 grade 3 pain in the RT+P group and 1 grade 3 radiodermatitis in the RT-only group), and there were no differences in terms of toxicity between the RT-only and the RT+P groups. No cardiac or pulmonary adverse event was reported during RT. With a median follow-up of 12 months (10-26), no patient relapsed. Conclusions: In this study of limited size, the authors did not find a difference between the RT-only and RT+P groups in terms of toxicity. More studies and longer follow-up may add to the strength of this evidence.

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre.

PURPOSE: Ultra-hypofractionation breast radiotherapy is a safe alternative to moderate hypofractionation. This study reports the results of two ultrahypofractionated regimens used in clinical practice in a high-volume radiotherapy center in terms of efficacy and of tolerance. METHODS: we included all patients treated in an adjuvant setting with five fractions after breast conserving surgery (BCS), for a histologically-confirmed invasive or in situ breast carcinoma. Radiotherapy regimens after BCS were either a 5-week schedule with 5 weekly fractions of 5,7 Gy or a one-week schedule with 5 daily fractions of 5,2 Gy. Adverse events were recorded and local-relapse free survival (LRFS), locoregional-relapse free survival (LRRFS), metastasis-free survival (MFS), for breast-cancer specific survival (BCSS) and overall survival (OS) were evaluated. RESULTS: Between December 2014 and December 2022, 396 patients (400 breasts) were treated with ultrahypofractionated radiotherapy. Five-year LRFS was 98.8% (95% confidence interval: 97.1%-100%), and 5-year OS was 96.0% (95%CI: 92.6-99.5%). Age was statistically associated with OS in univariate analysis (HR: 1.16, 95%CI: 1.04-1.42, p = .01). Four patients (1.0%) experienced acute grade 3 radiation-induced adverse events, and 8 patients (2.3%) acute grade 2 toxicities. Twenty-three patients (5.8%) experienced late toxicity, all of them being graded as grade 1. The use of the 5.7 Gy-weekly-fraction regimen and the delivery of a tumor bed boost were significantly associated with acute radiodermatitis (p < .01; p = .02; respectively) and late fibrosis (p < .01; p = .049; respectively). CONCLUSIONS: ultrahypofractionated radiotherapy was associated with an excellent tumor control rate in our 'real-life' cohort with low-risk breast cancer patients. However, delivery of a tumor bed boost and using weekly 5.7-Gy fractions were associated with an increased risk of acute and late cutaneous toxicities.

Outcomes following brachytherapy boost for intermediate- and high-risk prostate cancer: A retrospective bicenter study by the SFRO brachytherapy group.

INTRODUCTION: Radiotherapy dose escalation improves biochemical control in intermediate- or high-risk prostate cancer. Brachytherapy boost was shown to further improve biochemical control compared to radiotherapy alone in three randomized trials. The SFRO brachytherapy group sought to evaluate the efficacy and toxicity of BT-boost for intermediate and high-risk prostate cancer in real life, and to determine prognostic factors for efficacy and toxicity. MATERIAL AND METHOD: A retrospective study was conducted, including all patients with intermediate- or high-risk prostate cancer treated with a combination of external beam radiotherapy (EBRT) and high dose-rate brachytherapy boost (HDR-BB), from 2006 until December 2019 at two centers. Patient characteristics, initial disease, treatment and follow-up were collected. RESULTS: 709 patients from two centers were analyzed given a short follow-up in the other centers. Out of those, 277 were intermediate risk (170 favorable and 107 unfavorable) and 432 were high risk. The median EBRT and HDR-BB doses were 46 Gy (35-50) and 14 Gy (10-20). After a median follow-up of 62 months, biochemical control at 5 years was 87.5 % for the overall population, 91 % and 85 % for intermediate- and high-risk cancers, respectively. At 5 years, biochemical and clinical relapse-free survival, metastasis-free survival and local control rates were 83 %, 90 % and 97 % respectively. 5-years overall survival was 94 %. Late grade 2 or higher GU or GI toxicity was found in 36 patients (5 %) and 9 patients (1.3 %). CONCLUSION: This bicenter analysis shows the efficacy and tolerability of HDR-BB as a complement to external radiotherapy. Further improvements such as combination with new hormonal agents or new brachytherapy-radiotherapy fractionation regimens are warranted to improve further the outcomes and therapeutic ratio.

[Application in France of the 2021 European recommendations on endometrial cancer]. / Application en France des recommandations européennes 2021 sur le cancer de l'endomètre.

The latest European recommendations of the European Societies of Gynecological Oncology (ESGO), Radiotherapy and Oncology (ESTRO) and Anatomopathology (ESP) concerning the management of patients with endometrial cancer were published in 2021. On behalf of the French Society of Gynecologic Oncology (SFOG) and the SFOG campus, we wish to summarize for the French-speaking readership the main measures with a more specific application for France. We also incorporate data from a Delphi survey conducted with a panel of French and French-speaking Swiss experts. The data presented in this article relate to histo-molecular characteristics, radiological data of endometrial cancer, and management of low-risk, intermediate-risk, intermediate-high-risk, and metastatic cancers. The aim of this review article is to show the application of the latest international recommendations to clinicians and pathologists for the implementation of these recommendations.

Stereotactic Radiation Therapy versus Brachytherapy: Relative Strengths of Two Highly Efficient Options for the Treatment of Localized Prostate Cancer.

Stereotactic body radiation therapy (SBRT) has become a valid option for the treatment of low- and intermediate-risk prostate cancer. In randomized trials, it was found not inferior to conventionally fractionated external beam radiation therapy (EBRT). It also compares favorably to brachytherapy (BT) even if level 1 evidence is lacking. However, BT remains a strong competitor, especially for young patients, as series with 10-15 years of median follow-up have proven its efficacy over time. SBRT will thus have to confirm its effectiveness over the long-term as well. SBRT has the advantage over BT of less acute urinary toxicity and, more hypothetically, less sexual impairment. Data are limited regarding SBRT for high-risk disease while BT, as a boost after EBRT, has demonstrated superiority against EBRT alone in randomized trials. However, patients should be informed of significant urinary toxicity. SBRT is under investigation in strategies of treatment intensification such as combination of EBRT plus SBRT boost or focal dose escalation to the tumor site within the prostate. Our goal was to examine respective levels of evidence of SBRT and BT for the treatment of localized prostate cancer in terms of oncologic outcomes, toxicity and quality of life, and to discuss strategies of treatment intensification.

Efficacy and toxicity following salvage high-dose-rate brachytherapy for locally recurrent prostate cancer after radiotherapy.

INTRODUCTION: The management of local relapse after prostate cancer radiotherapy is frequently based on androgen deprivation therapy. The aim of the study was to report Gustave Roussy's experience with salvage prostate brachytherapy. PATIENTS AND METHODS: All cases of localized prostate cancer presenting in an irradiated area who received salvage high dose rate (HDR) brachytherapy from 2013 to 2020 were retrospectively reviewed. RESULTS: A total of 64 patients were included. Median follow up was 30.5 months. Median initial EBRT dose was 70 Gy [Q1-Q3: 70 - 74]. Median PSA at brachytherapy was 6.8 ng/mL [Q1-Q3: 4.4 - 8.7] with a median interval between first and salvage irradiation of 10 years [Q1-Q3: 6.9 - 12.6]. The modality of the first irradiation was an exclusive EBRT in 73% of the cases, mostly with a 3D technique (82%). Dose prescription was two fractions of 12 Gy or 13 Gy associated with androgen deprivation therapy for 63% of the patients. About 23% of the patients were castrate-resistant. Disease free survival at 2 years was 58% in the whole population and 66% in hormone sensitive patients. The only factors associated with disease free survival on multivariate analysis was a high-risk disease at initial diagnosis (HR = 3.59, IC95 [1.75; 7.39], p = 0.0005). Grade 3 urinary and rectal toxicities occurred in 1.5% and 1.5% of the patients, respectively. CONCLUSION: HDR salvage brachytherapy seems to be a safe option for patients presenting with an isolated local relapse of prostate cancer.

Brachytherapy for the Conservative Treatment of Female Peri-Urethral Carcinoma.

Introduction: Peri-urethral cancers (PUC) are rare tumors. Brachytherapy (BT), either monotherapy or combined with radiation therapy, is a preferred treatment option to spare the morbidity of surgery and achieve organ preservation. We report, to the best of our knowledge, the largest experience of brachytherapy among women with PUC. Patients and Methods: This is a retrospective review of the medical records of female patients with PUC who underwent low- or pulse-dose-rate BT with or without external beam radiotherapy at Gustave Roussy between 1990 and 2018. Patients were categorized according to the treatment intention into a primary and recurrent group. The Kaplan-Meier method was used for survival analysis, and the Cox proportional-hazard model was used for univariate analysis. Brachythewharapy-related adverse events were reported according to Common Terminology Criteria for Adverse Events version 4. Results: We identified 44 patients with PUC who underwent BT. Of the 44 patients, 22 had primary tumors and 22 had recurrent tumors. Histologies were mainly adenocarcinoma (n = 20) and squamous cell carcinoma (n = 14). The median prescribed dose was 60 Gy for the 24 patients treated with BT alone and 20 Gy (IQ range: 15-56.25 Gy) for the 20 patients treated with BT in combination with EBRT. With a median follow-up of 21.5 months (range 7.5-60.8), a total of six patients experienced local relapse (17.5%). The 2-year overall survival probability was 63% (95%CI: 49.2-81.4%). The most common toxicities were acute genito-urinary grade 1-2 toxicities. At the last follow-up, four patients experienced focal necrosis. Conclusions: In this cohort of women with PUC undergoing BT, we observed an 80% probability of local control with acceptable morbidity. Though survival was poor, with high metastatic relapse probability, BT was useful to focally escalate the dose and optimize local control in the context of an organ sparing strategy.

Resident training in brachytherapy in France: A 10-year update after the first survey of SFJRO members.

Purpose: A previous survey conducted in 2012 showed that 82% of radiation oncology residents felt they were not receiving optimal brachytherapy training. With almost 10 years of hindsight, the aim was to update these results. Material and methods: An anonymized questionnaire based on the 2012 survey was submitted to the 161 French residents enrolled in the 2021 French Society of Young Radiation Oncologists (Société Française des Jeunes Radiothérapeutes Oncologues - SFJRO) national brachytherapy courses. Results: With a participation rate of 73%, 86% of the residents were interested in brachytherapy, but 80% consider their training in brachytherapy insufficient. 88% and 69% of the residents stated that they knew gynecological and prostate brachytherapy indications correctly, respectively. The residents have achieved proficiency in the technique of brachytherapy of vaginal vault in 36% (compared with 21% in 2012), utero-vaginal in 13% (12% in 2012), including 4% with interstitial implants, and prostate in only 4% (4% in 2012). In their brachytherapy internships, 18% of the residents declared having no role or an observational role. The main obstacles to training were the need to go to several centers to see several indications (85%), lack of brachytherapy activity in the center (72%), and the difficulty of freeing themselves from hospital duties (71%). Conclusions: With results globally stable compared with 2012, brachytherapy training needs improvement. In the absence of a mandatory internship in a reference center or dedicated fellowships, residents must have protected access to training sites by favoring inter-hospital exchanges.

Venezia applicator with oblique needles improves clinical target volume coverage in distal parametrial tumor residue compared to parallel needles only.

PURPOSE: Residual distal parametrial involvement after radiochemotherapy is a true challenge for brachytherapists since the width and asymmetry of high-risk clinical target volume (HR-CTV) are difficult to cover properly with a standard implant. MATERIAL AND METHODS: Dosimetric plans of five patients treated with Venezia advanced gynecological applicator at our institution were reviewed. For each patient, we compared the original plan with a new plan where oblique needles were removed and re-optimized manually. Optimization process was halted when EQD210 D90 HR-CTV reached 90 Gy, when one hard constraint to organs at risk (OARs) was reached according to the EMBRACE II protocol, or when dose-rate of one of OARs exceeded 0.6 Gy/h. RESULTS: Tumors were large; median HR-CTV volume was 64 cc and median distance between tandem and outer contour of HR-CTV was 40 mm. For the five patients, HR-CTV EQD210 D90 was superior in the plan using oblique needles, with a median difference of 6.5 Gy (range, 1.7-8.5 Gy). Median D90 HR-CTV and intermediate-risk CTV (IR-CTV) were significantly increased with oblique needles: 85.9 Gy (range, 83.2-90.3 Gy) vs. 81.5 Gy (range, 77.4-84 Gy), and 68.7 Gy (range, 66.3-72.3 Gy) vs. 67 Gy (range, 64.3-69.1 Gy), p = 0.006 for both. There were no significant differences in the dose to OARs. Plans with only parallel needles had less favorable dose distribution, with cold spots on the outer parametria and higher vaginal activation to compensate parametrial coverage in its inferior part. CONCLUSIONS: VeneziaTM applicator permits reproducible application to increase CTV coverage in patients with distal parametrial tumor residue during brachytherapy, while maintaining acceptable dose to OARs.

Palliation of dysphagia in metastatic oesogastric cancers: An international multidisciplinary position.

Malignant dysphagia is the most common symptom in advanced oesogastric cancers patients. Relief of dysphagia allows quality of life improvement, nutritional replenishment and potentially improves prognosis. Chemotherapy alone is effective and should be prioritised in patients with metastatic disease a good performance status, and its impact on dysphagia should be determined before further interventions are planned. Regarding local treatments, the insertion of a covered self-expandable metallic stent is the most commonly used alternative, as it allows for the rapid relief of severe dysphagia. Although several randomised trials have highlighted the role of oesophageal brachytherapy, this technique is often not easily accessible. Contemporary trials are ongoing to better define the role of external radiation therapy. While awaiting these results, external radiation therapy can be considered as a second-best option for patients with a life-expectancy > 3 months. It is important to offer nutritional support and to integrate quality of life measures in the palliative management of dysphagia. This multidisciplinary international position paper aims to propose a decision-making process and highlight randomised trials for the management of malignant dysphagia in metastatic oesogastric cancer patients.

Hypnosedation for endocavitary uterovaginal applications: A pilot study.

PURPOSE: Implantations for uterovaginal brachytherapy are usually performed under general or spinal anesthesia, which are not without risk. As it is a rather short procedure and since postoperative pain is minimal, hypnosedation was proposed to selected patients requiring endocavitary applications as part of their routine treatment. METHODS AND MATERIALS: Consecutive patients requiring intracavitary uterovaginal brachytherapy from January to October 2019 were included if they accepted the procedure. A premedication was systematically administered. Hypnosedation was based on an Ericksonian technique. The procedure was immediately interrupted if the patient requested it, in cases of extreme anxiety or pain. Procedure was in that case rescheduled with a "classical" anesthesia technique. RESULTS: A total of 20 patients were included. Four patients had to be converted toward a general anesthesia: one because of a fibroma on the probe's way and three young patients with a very anteverted/retroverted uterus that was painful at every mobilization. Mean and maximum pain scores during implant were 2.9/10 and 5.1/10, respectively. The most painful maneuver was cervical dilation for 45% of the patients, followed by mold insertion in 40% of cases. About 85% of the patients declared that hypnosis helped them relax; 90% of the patients would recommend the technique. No procedure-related complication occurred. CONCLUSION: With a 70% success rate (correct implant with mean pain and anxiety scores < 5), one can conclude that uterovaginal brachytherapy implantation under hypnosedation is feasible and received a high satisfaction rate from the patients. This technique may reduce overall treatment time in a context of difficult access to the OR and to anesthesiologists, while reducing anesthetic drugs resort and postoperative nausea.

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.

Stereotactic ablative radiotherapy and systemic treatments for extracerebral oligometastases, oligorecurrence, oligopersistence and oligoprogression from lung cancer.

BACKGROUND: Stereotactic irradiation (SBRT) is a standard of care for inoperable stage I lung cancer and brain oligometastases from lung cancer but is controversial for extracranial oligometastases. We assessed outcomes of lung cancer patients with extracranial metastases in oligometastatic, oligorecurrent, oligopersistent and oligoprogressive settings ("oligometastatic spectrum") under strategies using SBRT +/- systemic treatments. METHODS: A retrospective multicentric study of consecutive lung cancer adult patients with 1-5 extracranial metastases treated with SBRT was conducted. RESULTS: Of 91 patients (99 metastases, median age 63, 64.8% adenocarcinomas, 19.8% molecular alterations), 11% had oligometastases, 49.5% oligorecurrence, 19.8% oligopersistence and 19.8% oligoprogression. Of 36% of patients under systemic treatments at initiation of SBRT, systemic treatment interruption was performed in 58% of them. With median follow up of 15.3 months, crude local control at irradiated metastases was 91%, while median distant progression-free survival (dPFS) and overall survival were 6.3 and 28.4 months (2-year survival 54%). Initial nodal stage and oligometastatic spectrum were prognostic factors for dPFS; age, initial primary stage and oligometastatic spectrum were prognostic factors for survival on multivariate analysis. Patients with oncogene-addicted tumors more frequently had oligoprogressive disease. Repeat ablative irradiations were preformed in 80% of patients who had oligorelapses. Worst acute toxicities consisted of 5.5% and one late toxic death occurred. CONCLUSION: The oligometastatic spectrum is a strong prognosticator in patients undergoing SBRT for extracranial metastases. Median survival was over two years but dPFS was about 6 months. Continuation of systemic therapy in oligoprogressive patients should be investigated.

Impact of suboptimal tandem implantation on local control and complications in intracavitary brachytherapy for cervix cancer.

PURPOSE: Correct tandem implantation for cervix cancer intracavitary brachytherapy may be challenging. We investigated whether suboptimal implantation can be related to patient and disease characteristics and may result in subsequent underutilization of brachytherapy in cervical cancer. METHODS AND MATERIALS: Consecutive cervix cancer patients referred for intracavitary brachytherapy after external beam radiation therapy performed in several general hospitals from 2013 to 2017 were included. RESULTS: In 172 patients having 301 procedures, 95 implantations were suboptimal (15% inadequate tandem insertions, 10% subserosal insertion, and 6% uterine perforation on postimplant CT scan). Risk factors were age, myometrium invasion, and uterine retroversion. Median followup was 21 months. Three-year local control and survival rates were 72% and 85%, respectively. Forty-seven patients (27%) failed to receive brachytherapy. Failure to perform brachytherapy was associated with poorer local control (OR = 0.34 [0.17-0.67], p = 0.001). By contrast, suboptimal implantation did not increase local failure or toxicity rates in patients undergoing brachytherapy. No peritoneal carcinomatosis occurred after uterine perforation in our cohort. CONCLUSIONS: Suboptimal implantation was frequent. In the absence of image guidance during implantation, conversion to other treatment modalities (including external beam radiation therapy) due to insertion difficulties resulted in worse local control. With optimization, however, suboptimal brachytherapy implantation did not result in suboptimal dose coverage or poorer local control. Failure to perform a brachytherapy boost correlates with increased local failure risk in patients with cervix cancer, whereas tandem malposition does not. Real-time intraoperative ultrasound guidance may be useful to reduce uterine perforation rates and thus increase brachytherapy use.

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.

Oral vinorelbine-based concomitant chemoradiotherapy in unresectable stage III non-small cell lung cancer: a systematic review.

INTRODUCTION: Cisplatin-based chemotherapy administered concomitantly to thoracic radiotherapy is the treatment recommended by the European guidelines for fit patients with unresectable stage III non-small cell lung cancer (NSCLC). Cisplatin may be combined with etoposide, vinorelbine or other vinca alkaloids, which act also as radiation sensitizers. Initially administered intravenously, vinorelbine is also available as oral formulation and is the only orally available microtubule-targeting agent. In addition, the oral formulation avoids the risk of extravasation and phlebitis. Areas covered: A literature search has been performed for articles reporting phase II-III trials aimed to evaluate efficacy and safety of oral vinorelbine-based chemoradiotherapy in unresectable locally advanced NSCLC. Expert commentary: In a series of trials with various protocols published from 2008 to 2018, mostly phase II studies, oral vinorelbine demonstrated a significant activity in concomitant chemoradiotherapy for unresectable locally advanced NSCLC typically as part of combination schedules with cisplatin. Main toxicities were hematologic (neutropenia and anemia); non-hematological toxicities included esophagitis and gastro-duodenal adverse events. Large prospective phase III trials are needed to confirm the role of vinorelbine-based chemotherapy associated to thoracic radiotherapy in unresectable stage III NSCLC and more particularly trials with metronomic oral vinorelbine.

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.

[Definitions of oligometastatic disease and new treatment concepts]. / Nouvelles définitions de la maladie oligométastatique et nouveaux concepts de prise en charge globale de la maladie métastatique.

The definition of oligometastatic disease has evolved into distinct intermediate stages of different prognosis between single metastasis and polymetastatic disease. We assessed the therapeutic impact of such clinical definitions based on a review of the literature. Increasingly advanced stages of the metastatic disease with some prominent oligometastatic targets can be treated with stereotactic irradiation with ablative intent owing to its excellent tolerance profile. Used in different settings, metastatic ablation can either prolong progression free survival, delay change of systemic therapy or delay the time to symptoms. It may also improve survival, quality of life and health care costs in some situations. While most approaches have studied metastases by anatomic site rather than histology, combined systemic-ablative local treatment approaches are being developed for cancers of similar behavior. Biology-driven and imaging-oriented approaches are being investigated to better identify metastatic profiles for treatment guidance.