Publications by authors named "Cyrus Chargari"

288 Publications

Implementation of Image-Guided Brachytherapy for Pediatric Vaginal Cancers: Feasibility and Early Clinical Results.

Cancers (Basel) 2022 Jul 1;14(13). Epub 2022 Jul 1.

Department of Radiation Oncology, Gustave Roussy Cancer Campus, 94800 Villejuif, France.

Brachytherapy (BT) has a major role in pediatric cancers of the lower genital tract, as part of a multimodal organ conservative strategy. Scarce data are available on the location of image-guided BT. Medical records of all consecutive girls treated in our center between 2005 and 2020 for a vaginal tumor with exclusive image-guided PDR-BT were retrospectively examined, with a focus on treatment parameters, patient compliance, and clinical outcome, including analysis of local control, survival and late toxicity rates. Twenty-six patients were identified, with a median age of 25 months. Histological types were rhabdomyosarcoma, malignant germ cell tumor (MGCT) and clear cell adenocarcinoma in 18 (69%), 7 (27%) and 1 (4%) patients, respectively. Ten (33%) patients had prior surgery and 25 (96%) received chemotherapy prior to BT. The median prescribed dose was 60 Gy through pulses of 0.42 Gy. Global compliance was satisfactory, but three (12%) patients required replanning because of applicator displacement. After a median follow-up of 47.5 months, one patient with MGCT referred for salvage treatment of a local recurrence had a local and metastatic relapse. The local control rate probability was 96% at the last follow-up. Late toxicity rates ≥ grade 2 and ≥ grade 3 were reported in 23% and 11%, respectively, with gynecological toxicities being the most frequent side effect. Two patients required dilatation for vaginal stenosis. PDR-BT allowed similar local control compared to the historical low-dose rate technique. An indirect comparison suggests fewer treatment-related toxicities by integrating image guidance and optimization capabilities, but longer follow-up is necessary. Due to the rarity of the disease and the technical aspects of BT in these very young patients, referral to specialized high-volume centers is recommended.
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http://dx.doi.org/10.3390/cancers14133247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265517PMC
July 2022

Imaging approaches and radiomics: toward a new era of ultraprecision radioimmunotherapy?

J Immunother Cancer 2022 Jul;10(7)

Department of Radiation Oncology, Gustave Roussy, Villejuif, France

Strong rationale and a growing number of preclinical and clinical studies support combining radiotherapy and immunotherapy to improve patient outcomes. However, several critical questions remain, such as the identification of patients who will benefit from immunotherapy and the identification of the best modalities of treatment to optimize patient response. Imaging biomarkers and radiomics have recently emerged as promising tools for the non-invasive assessment of the whole disease of the patient, allowing comprehensive analysis of the tumor microenvironment, the spatial heterogeneity of the disease and its temporal changes. This review presents the potential applications of medical imaging and the challenges to address, in order to help clinicians choose the optimal modalities of both radiotherapy and immunotherapy, to predict patient's outcomes and to assess response to these promising combinations.
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http://dx.doi.org/10.1136/jitc-2022-004848DOI Listing
July 2022

Practice changing data and emerging concepts from recent radiation therapy randomised clinical trials.

Eur J Cancer 2022 08 29;171:242-258. Epub 2022 Jun 29.

Gustave Roussy, Département de Radiothérapie, F-94805, Villejuif, France; Université Paris-Saclay, Faculté de Médecine, F-94270, Le Kremlin Bicêtre, France; Université Paris-Saclay, Inserm U-1030, Laboratoire de Radiothérapie Moléculaire et d'Innovation Thérapeutique, F-94805, Villejuif, France. Electronic address:

Introduction: Oncology treatments are constantly and rapidly evolving. We aimed at highlighting the latest radiation therapy practice changing trials and emerging concepts, through an overview of recent randomised clinical trials (RCTs).

Materials And Methods: Requests were performed in the Medline database to identify all publications reporting radiation therapy RCTs from 2018 to 2021.

Results: Recent RCTs sustained the role of newer combinatorial strategies through radioimmunotherapy for early stage or metastatic lung cancer, newer pro-apoptotic agents (e.g. debio 1143 in locoregionally advanced head and neck squamous cell carcinoma) or nanoparticles (e.g. NBTXR3 in locally advanced soft-tissue sarcoma). High-tech radiotherapy allows intensifying treatments and gaining ground in some indications through the development of stereotactic body radiotherapy for example. First randomised evidence on personalised radiation therapy through imaging-based (FDG positron emission tomography-computed tomography for lung cancer or early stage unfavourable Hodgkin lymphoma, PMSA positron emission tomography-computed tomography or magnetic resonance imaging for high-risk prostate cancer) or biological biomarkers (PSA for prostate cancer, HPV for head and neck cancer, etc) were conducted to more tailored treatments, with more favourable outcomes. Patients' quality of life and satisfaction appeared to be increasing aims. RCTs have validated (ultra)hypofractionated schemes in many indications as for breast, prostate or rectal cancer, resulting in equivalent outcomes and toxicities, more convenient for patients and favouring shared decision making.

Conclusion: Radiation therapy is a dynamic field of research, and many RCTs have greatly impacted therapeutic standards over the last years. Investments in radiotherapy research should facilitate the transfer of innovation to clinic.
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http://dx.doi.org/10.1016/j.ejca.2022.04.038DOI Listing
August 2022

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) Consensus Statements on Pre-invasive Vulvar Lesions.

J Low Genit Tract Dis 2022 Jul 21;26(3):229-244. Epub 2022 Jun 21.

Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Abstract: The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).
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http://dx.doi.org/10.1097/LGT.0000000000000683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232287PMC
July 2022

Providing Patients with Locally Advanced Cervical Cancer Access to Brachytherapy: Experience from a Referral Network for Women Treated in Overseas France.

Cancers (Basel) 2022 Jun 14;14(12). Epub 2022 Jun 14.

Radiation Oncology Department, Gustave Roussy Cancer Campus, 94805 Villejuif, France.

Image-guided adaptive brachytherapy (IGABT) is part of the standard of care for locally advanced cervical cancer (LACC). Access to IGABT is limited in many regions, thus leading to treatment care disparities. We report the experience of a referral network for women with LACC between radiotherapy facilities in Overseas France and Gustave Roussy. This is a retrospective review of patients with LACC referred to Gustave Roussy, for pulsed-dose-rate (PDR) image-guided adaptive BT after initial radiation therapy in the French overseas between 2014 and 2021. Sixty-four patients were eligible to receive IGABT. Overall treatment time (OTT) was 60.5 days (IQR: 51-68.5). The median follow-up time was 17 months. At two years, estimated probabilities of LC, progression-free survival, and overall survival (OS) were 94.6% (95% CI: 88.9-100.0%), 72.7% (95% CI: 61.1-86.5%), and 82.5% (95% CI: 72.0-94.5%). In multivariable analysis, a D90CTVHR < 85GyEQD2 and a CTVHR volume > 40 cm were significant for poorer PFS ( = 0.001 and = 0.009, respectively) and poorer OS ( = 0.004 and = 0.004). The centralization of this advanced technique to expert centers requires a well-defined workflow and appropriate dimensioning of resources to minimize OTT.
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http://dx.doi.org/10.3390/cancers14122935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221527PMC
June 2022

Long-term urological complications after conservative local treatment (surgery and brachytherapy) in children with bladder-prostate rhabdomyosarcoma: A single-team experience.

Pediatr Blood Cancer 2022 08 6;69(8):e29532. Epub 2022 Jan 6.

Department of Pediatric Surgery, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Saclay University, Le Kremlin-Bicêtre, France.

Background: Outcome of children with bladder-prostate rhabdomyosarcoma (RMS) has improved with multimodal therapies, including surgery and/or radiotherapy for local treatment. Our aim was to report long-term urological complications after a conservative approach combining conservative surgery and brachytherapy.

Patients And Methods: Eighty-six patients, free of disease, were retrospectively reviewed. Symptoms related to urinary tract obstruction, incontinence, infection, and lithiasis were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Only symptomatic patients underwent urodynamic studies. Risk factors for complications were analyzed.

Results: There were 76 males and 10 females. The median follow-up was 6.3 years (18 months to 24 years). Complications occurred after a median follow-up of 5 years (0-21). Twenty-two patients (26%) had long-term urological complications. Urinary tract obstruction was found in 15 patients (17%) and urinary incontinence in 14 patients (16%). Recurrent urinary tract infection occurred in four patients and urinary lithiasis in four (5%). The underlying physiopathology included bladder dysfunction in 15 patients (17%), urethral stenosis in six (7%), and ureterovesical junction stenosis in five (6%). On univariate analysis, posterior bladder wall dissection (p = .001), bladder neck trigone dissection (p = .010), and partial prostatectomy (p = .023) were significantly associated with an increased risk of bladder dysfunction; on multivariate analysis, only age ≤2 years (p = .028) at operation and posterior bladder wall dissection (p = .006) were found to be significant.

Conclusion: The conservative surgical approach combined with brachytherapy for bladder-prostate RMS leads to long-term urological complications in 26% of survivors. Optimizing brachytherapy doses for young children and establishing a clear and long-term follow-up protocol could help to reduce these complications.
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http://dx.doi.org/10.1002/pbc.29532DOI Listing
August 2022

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) consensus statements on pre-invasive vulvar lesions.

Int J Gynecol Cancer 2022 Jun 21. Epub 2022 Jun 21.

Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).
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http://dx.doi.org/10.1136/ijgc-2021-003262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279839PMC
June 2022

Robot-Assisted Surgery vs Robotic Stereotactic Body Radiotherapy in Prostate Cancer: A Cost-Utility Analysis.

Front Oncol 2022 24;12:834023. Epub 2022 May 24.

Département d'économie de la santé, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.

Prostate cancer is the most common men cancer in France. Continuous progress in oncology led to develop robot-assisted Radical Prostatectomies (rRP) and robot-assisted stereotactic body radiotherapy (rSBRT). The present study aims at comparing economic and clinical impacts of prostate cancer treatments performed either with rSBRT or rRP in France. A Markov model using TreeAge Pro software was chosen to calculate annual costs; utilities and transition probabilities of localized prostate cancer treatments. Patients were eligible for radiotherapy or surgery and the therapeutic decision was a robot-assisted intervention. Over a 10-year period, rSBRT yielded a significantly higher number of quality-adjusted life years than rRP (8.37 vs 6.85). In France, rSBRT seemed more expensive than rRP (€19,475 vs €18,968, respectively). From a societal perspective, rRP was more cost-saving (incremental cost effectiveness ratio = €332/QALY). The model was sensitive to variations of costs of the initial and recurrence state in one-way sensitivity analyses. Robot-assisted stereotactic body radiotherapy seems more cost-effective than Radical Prostatectomy in terms of QALY despite the slightly higher initial cost due to the use of radiotherapy. It would be interesting to conduct comparative quality of life studies in France over longer periods of time.
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http://dx.doi.org/10.3389/fonc.2022.834023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172203PMC
May 2022

Current Standards in the Management of Early and Locally Advanced Cervical Cancer: Update on the Benefit of Neoadjuvant/Adjuvant Strategies.

Cancers (Basel) 2022 May 16;14(10). Epub 2022 May 16.

Department of Radiation Oncology, Gustave Roussy Comprehensive Cancer Centre, 94800 Villejuif, France.

Globally, cervical cancers continue to be one of the leading causes of cancer-related deaths. The primary treatment of patients with early-stage disease includes surgery or radiation therapy with or without chemotherapy. The main challenge in treating these patients is to maintain a curative approach and limit treatment-related morbidity. Traditionally, inoperable patients are treated with radiation therapy solely and operable patients undergo upfront surgery followed by adjuvant (chemo) radiotherapy in cases with poor histopathological prognostic features. Patients with locally advanced cervical cancers are treated with concurrent chemoradiotherapy followed by an image-guided brachytherapy boost. In these patients, the main pattern of failure is distant relapse, encouraging intensification of systemic treatments to improve disease control. Ongoing trials are evaluating immunotherapy in locally advanced tumours following its encouraging efficacy reported in the recurrent and metastatic settings. In this article, clinical evidence of neoadjuvant and adjuvant treatments in cervical cancer patients is reviewed, with a focus on potential strategies to improve patients' outcome and minimize treatment-related morbidity.
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http://dx.doi.org/10.3390/cancers14102449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139662PMC
May 2022

Endometrioid Borderline Ovarian Tumor: Clinical Characteristics, Prognosis, and Managements.

Ann Surg Oncol 2022 May 19. Epub 2022 May 19.

Department of Gynaecologic Surgery, Gustave-Roussy, Villejuif, France.

Background: Endometrioid borderline ovarian tumor (EBOT) is a rare subtype of borderline ovarian malignancies. This study was designed to determine the prognosis of a series of EBOT.

Methods: This is a retrospective review of patients with EBOT treated in or referred to our institutions and a centralized, histological review by a reference pathologist. Data on the clinical characteristics, management (surgical and medical), and oncologic outcomes of patients were required for inclusion.

Results: Forty-eight patients were identified. Median age was 52 years (range 14-89). Fourteen patients underwent a conservative surgery and 32 a bilateral salpingo-oophorectomy (unknown in 2 cases). Two patients had bilateral tumors. Forty-three patients had stage I disease, and five patients had stage II disease (10%). Stromal microinvasion and intraepithelial carcinoma was observed in 6 (12%) and 13 (27%) patients respectively. Endometriosis was histologically associated in 12 patients (25%). Synchronous endometrial disease was found in 7 (24%) of 29 patients with endometrial histological evaluation. The median follow-up was 72 months (range 6-146). Two patients developed a recurrence after cystectomy in form of borderline disease (5%). No death related to EBOT occurred.

Conclusions: Peritoneal restaging surgery should be performed if not realized initially, because 5% of EBOTS are diagnosed at stage II-III. Fertility-sparing surgery seems a safe option in selected patients. Because synchronous endometrial diseases, including endometrial carcinoma are frequent, systematic hysterectomy (or endometrial sampling in case of fertility-sparing surgery) is mandatory. Prognosis is generally excellent. Recurrence is a rare event (6%), but it can occur in the form of invasive disease.
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http://dx.doi.org/10.1245/s10434-022-11893-7DOI Listing
May 2022

Neoadjuvant chemotherapy in fertility-sparing management of FIGO 2018 stage IB2 cervical cancer.

Int J Gynecol Cancer 2022 05 3;32(5):680-685. Epub 2022 May 3.

Department of Gynecological Surgery, Gustave Roussy, Villejuif, Île-de-France, France

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http://dx.doi.org/10.1136/ijgc-2021-003293DOI Listing
May 2022

Brachytherapy for Pediatric Patients at Gustave Roussy Cancer Campus: A Model of International Cooperation for Highly Specialized Treatments.

Int J Radiat Oncol Biol Phys 2022 Jul 9;113(3):602-613. Epub 2022 Mar 9.

Pediatric Surgery, Hôpital Universitaire Robert-Debré, Assistance Publique de Hôpitaux de Paris, Paris, France.

Purpose: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers.

Methods And Materials: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy.

Results: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy.

Conclusions: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability.
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http://dx.doi.org/10.1016/j.ijrobp.2022.03.003DOI Listing
July 2022

Combined modality including novel sensitizers in gynecological cancers.

Int J Gynecol Cancer 2022 03;32(3):389-401

Department of Radiation Oncology, Gustave Roussy, Villejuif, France

Standard treatment of locally advanced gynecological cancers relies mainly on platinum-based concurrent chemoradiotherapy followed by brachytherapy. Current chemotherapeutic drugs are only transiently effective and patients with advanced disease often develop resistance and subsequently, distant metastases despite significant initial responses of the primary tumor. In addition, some patients still develop local failure or progression, suggesting that there is still a place for increasing the anti-tumor radiation effect. Several strategies are being developed to increase the probability of curing patients. Vaginal cancer and vulva cancer are rare diseases, which resemble cervical cancer in their histology and pathogenesis. These gynecological cancers are predominantly associated with human papilloma virus infection. Treatment strategies in other unresectable gynecologic cancers are usually derived from evidence in locally advanced cervical cancers. In this review, we discuss mechanisms by which novel therapies could work synergistically with conventional chemoradiotherapy, from pre-clinical and ongoing clinical data. Trimodal, even quadrimodal treatment are currently being tested in clinical trials. Novel combinations derived from a metastatic setting, and being tested in locally advanced tumors, include anti-angiogenic agents, immunotherapy, tumor-infiltrating lymphocytes therapy, adoptive T-cell therapy and apoptosis inducers to enhance chemoradiotherapy efficacy through complementary molecular pathways. In parallel, radiosensitizers, such as nanoparticles and radiosensitizers of hypoxia aim to maximize the effect of radiotherapy locally.
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http://dx.doi.org/10.1136/ijgc-2021-002529DOI Listing
March 2022

Role of Brachytherapy in the Postoperative Management of Endometrial Cancer: Decision-Making Analysis among Experienced European Radiation Oncologists.

Cancers (Basel) 2022 Feb 11;14(4). Epub 2022 Feb 11.

Klinik für Strahlentherapie und Onkologie, Universitätsklinikum Frankfurt, Goethe Universität, 60590 Frankfurt, Germany.

Background: There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT.

Methods: Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology.

Results: The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1-2 LVSI-negative disease. For 74-84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT.

Conclusions: There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1-2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic.
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http://dx.doi.org/10.3390/cancers14040906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869913PMC
February 2022

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

Cancers (Basel) 2022 Feb 8;14(3). Epub 2022 Feb 8.

Department of Radiation Oncology, Gustave Roussy Cancer Campus, 94800 Villejuif, France.

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. 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. 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 ( = 20) and squamous cell carcinoma ( = 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. 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.
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http://dx.doi.org/10.3390/cancers14030845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834286PMC
February 2022

Inoperable scalp cutaneous angiosarcoma: Complete response after definitive external beam radiation therapy - brachytherapy association.

Oral Oncol 2022 02 11;125:105715. Epub 2022 Jan 11.

Department of Radiation Oncology, Gustave Roussy, F-94805 Villejuif, France; Université Paris-Saclay, Faculté de Médecine, 94270 Le Kremlin-Bicêtre, France; Université Paris-Saclay, INSERM U1030, Molecular Radiotherapy, F-94805 Villejuif, France. Electronic address:

Effective treatments are scarce in non-operable scalp cutaneous angiosarcoma patients. Curative-intent definitive sequential IMRT and plesiobrachytherapy allowed complete response with limited side effect in two elder patients. This could represent a non-invasive therapeutic option for patients with locally advanced presentation.
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http://dx.doi.org/10.1016/j.oraloncology.2022.105715DOI Listing
February 2022

Risk Factors for Late Persistent Fatigue After Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer: An Analysis From the EMBRACE-I Study.

Int J Radiat Oncol Biol Phys 2022 04 25;112(5):1177-1189. Epub 2021 Nov 25.

Department of Radiation Oncology, Comprehensive Cancer Center, Medical University Hospital of Vienna, Vienna, Austria. Electronic address:

Purpose: This study aimed to evaluate patient- and treatment-related risk factors for late persistent fatigue within the prospective, multicenter EMBRACE-I study.

Methods And Materials: Fatigue was prospectively assessed (Common Terminology Criteria for Adverse Events, version 3) at baseline and during regular follow up in 993 patients with locally advanced cervical cancer after treatment with chemoradiotherapy and magnetic resonance imaging-guided brachytherapy. Risk factors for baseline and late persistent fatigue were evaluated with multivariable logistic regression. Late persistent fatigue was defined when either grade ≥1 or ≥2 was scored in at least half of the follow ups.

Results: The median follow-up time was 57 months. Baseline fatigue grade ≥1/≥2 (35.8%/6.3%, respectively) was associated with preexisting comorbidities, World Health Organization performance status, being underweight, severe pain, and tumor volume. Late persistent grade ≥1/≥2 fatigue (36.3%/5.8%, respectively) was associated with patient-related factors (baseline fatigue, younger age, obesity) along with the size of irradiated volumes and the level of radiation doses from external beam radiation therapy (EBRT) and brachytherapy (EBRT: V43Gy, V57Gy; EBRT + brachytherapy: V60Gy equivalent dose in 2-Gy fractions). Large-volume lymph node (LN) boost increased the risk for late persistent fatigue grade ≥2 by 18% and 5% in patients with and without baseline fatigue, respectively, compared with no LN boost. The risk for late persistent fatigue grade ≥1 increased by 7% and 4% with V43Gy <2000 cm³ versus >3000 cm³ in patients with and without baseline fatigue, respectively. Late persistent grade ≥1 fatigue occurred in 13% of patients without late persistent organ-related symptoms (gastrointestinal, genitourinary, and vaginal) versus 34% to 43%, 50% to 58%, and 73% in patients suffering from persistent symptoms involving 1, 2, or 3 organs, respectively.

Conclusions: Late persistent fatigue occurs in a considerable number of patients after chemoradiotherapy, and is associated with patient-related factors, the size of volumes irradiated to intermediate and high EBRT and brachytherapy doses, and other persistent organ-related morbidity. These findings support the importance of ongoing efforts to better tailor the target dose and reduce irradiation of healthy tissue without compromising target coverage, using highly conformal EBRT and brachytherapy techniques.
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http://dx.doi.org/10.1016/j.ijrobp.2021.11.022DOI Listing
April 2022

Cervical Cancer and Fertility-Sparing Treatment.

J Clin Med 2021 Oct 21;10(21). Epub 2021 Oct 21.

Department of Gynecologic Surgery, Gustave Roussy, 94800 Villejuif, France.

Radical hysterectomy with pelvic node dissection is the standard treatment for early-stage cervical cancer. However, the latter can be diagnosed at a young age when patients have not yet achieved their pregnancy plans. Dargent first described the vaginal radical trachelectomy for patients with tumors <2 cm. It has since been described a population of low risk of recurrence: patients with tumors <2 cm, without deep stromal infiltration, without lymphovascular invasion (LVSI), and with negative lymph nodes. These patients can benefit from a less radical surgery such as conization or simple trachelectomy with the evaluation of the pelvic node status. Tumors larger than 2 cm have a higher risk of recurrence and their treatment is a challenge. There are currently two options for these patients: abdominal radical trachelectomy or neoadjuvant chemotherapy (NACT), followed by fertility-sparing surgery. All patients who wish to preserve their fertility must be referred to expert centers.
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http://dx.doi.org/10.3390/jcm10214825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585101PMC
October 2021

Severity and Persistency of Late Gastrointestinal Morbidity in Locally Advanced Cervical Cancer: Lessons Learned From EMBRACE-I and Implications for the Future.

Int J Radiat Oncol Biol Phys 2022 03 20;112(3):681-693. Epub 2021 Oct 20.

Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.

Purpose: The purpose was to evaluate patient- and treatment-related risk factors for physician-assessed and patient-reported gastrointestinal (GI) symptoms after radio(chemo)therapy and image guided adaptive brachytherapy in locally advanced cervical cancer.

Methods And Materials: Of 1416 patients from the EMBRACE-I study, 1199 and 1002 were prospectively evaluated using physician-assessed (Common Terminology Criteria for Adverse Events [CTCAE]) and patient-reported (European Organization for Research and Treatment of Cancer [EORTC]) GI symptoms, respectively. CTCAE severe grade (grade [G] ≥3) events were pooled according to the location in the GI tract (anus/rectum, sigmoid, and colon/small bowel). CTCAE G ≥2 and EORTC "very much" and "quite a bit" plus "very much" scores (≥ "quite a bit") were analyzed for individual symptoms with Cox regression. Logistic regression was used for persistent G ≥1 and EORTC ≥ "quite a bit" symptoms, defined if present in at least half of follow-ups.

Results: The incidence of G ≥3 events was 2.8%, 1.8%, and 2.3% for G ≥3 anus/rectum, sigmoid, and colon/small bowel events, respectively. Among G ≥2 symptoms, diarrhea and flatulence were the most prevalent (8.5% and 9.9%, respectively). Among patient-related factors, baseline morbidity, increasing age, smoking status, and low body mass index were associated with GI symptoms to varying degrees. Among treatment-related factors, rectum D and the International Commission on Radiation Units and Measurements recto-vaginal reference point (ICRU RV-RP) correlated with G ≥3 anus/rectum events and moderate/persistent diarrhea, proctitis, bleeding, abdominal cramps, and difficulty in bowel control. Bowel D correlated with G ≥3 sigmoid and colon/small bowel events and moderate/persistent diarrhea and flatulence. For external beam radiation therapy (EBRT), prescription dose correlated with G ≥3 anus/rectum, diarrhea, and difficulty in bowel control. Patients with large lymph-node boost (V57Gy) were at higher risk for G ≥3 sigmoid events, moderate/persistent diarrhea, proctitis, and cramps.

Conclusions: The analysis showed that both EBRT and image guided adaptive brachytherapy contribute to GI symptoms after locally advanced cervical cancer treatment. Rectum D, ICRU RV-RP , and bowel D are risk factors for GI morbidity. The risk for various symptoms was lower with an EBRT prescription of 45 Gy than 50 Gy and increased with larger V57Gy.
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http://dx.doi.org/10.1016/j.ijrobp.2021.09.055DOI Listing
March 2022

[Surgical de-escalation in gynecologic oncology].

Bull Cancer 2021 Dec 7;108(12):1155-1161. Epub 2021 Oct 7.

Service de chirurgie gynécologique, Gustave-Roussy, 94805 Villejuif, France.

The evolution of knowledge in gynecologic oncology is leading to surgical de-escalation in several areas, particularly in lymph node staging. Sentinel lymph node biopsy that was initially used in low and intermediate risk endometrial cancer, has now been extended to high-intermediate and high-risk endometrial cancer. Sentinel lymph node biopsy plays also an important role in the nodal staging of early-stage cervical cancer. The radicality of hysterectomies in patients with early cervical cancer is under debate. Similarly, surgical staging with para-aortic lymphadenectomy in locally advanced cervical cancer should be performed only for few cases. Systematic pelvic and para-aortic lymphadenectomy in patients with advanced ovarian cancers is not recommended anymore.
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http://dx.doi.org/10.1016/j.bulcan.2021.06.012DOI Listing
December 2021

Second malignancy (SM) in prostate cancer patients treated with SBRT and other contemporary radiation techniques.

Radiother Oncol 2021 11 8;164:251-252. Epub 2021 Oct 8.

Radiation Oncology, Centre Charlebourg, La Garenne Colombe, France.

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http://dx.doi.org/10.1016/j.radonc.2021.10.001DOI Listing
November 2021

Clear Cell Borderline Ovarian Tumor: Clinical Characteristics, Prognosis, and Management.

Ann Surg Oncol 2022 Feb 1;29(2):1165-1170. Epub 2021 Oct 1.

Department of Gynaecologic Surgery, Gustave-Roussy, Villejuif, France.

Background: Clear cell borderline ovarian tumor (CCBOT) is one of the rarest subtypes of borderline ovarian malignancies. The aim of this study was to determine the prognosis of a series of CCBOT.

Patients And Methods: A retrospective review of patients with CCBOT treated or referred to our institutions. A centralized histological review by a reference pathologist and data on the clinical characteristics, management, and outcomes of patients were required for inclusion.

Results: Nineteen patients were identified. Median age was 62 (range 36-83) years. Four patients underwent a conservative surgery and 14 a bilateral salpingo-oophorectomy +/- hysterectomy (unknown in 1 case). One patient had bilateral tumor, and all cases were stage-I disease. All CCBOTs showed an adenofibromatous pattern. Stromal microinvasion was observed in seven cases and intraepithelial carcinoma in two cases. Endometriosis was histologically associated in one case. The median follow-up was 76 (range 6-231) months. No recurrence occurred. Two patients died of intercurrent disease.

Conclusions: Peritoneal staging procedures should always be associated, but restaging surgery could be omitted if there was no suspicious lesion in the peritoneum during initial surgery, since all patients reported had stage-I disease. Fertility-sparing surgery appears to be a safe alternative in young patients. Synchronous endometrial disorders with atypia are infrequent. Prognosis is generally excellent, and long-term risk of recurrence is low. The two recurrences described in literature occurred in stage-IC diseases, highlighting the importance of avoiding perioperative rupture.
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http://dx.doi.org/10.1245/s10434-021-10776-7DOI Listing
February 2022

[Fertility preservation in cervical cancer, analysis of 30 years of practice and immersion in future developments].

Gynecol Obstet Fertil Senol 2022 Jan 4;50(1):62-68. Epub 2021 Sep 4.

Département de chirurgie gynécologique, Institut Gustave Roussy, 114, rue Edouard Vaillant, 94805 Villejuif Cedex, France; Unité Inserm U 10-30, Gustave Roussy, Villejuif, France; Université Paris-Sud (Paris XI), Le Kremlin Bicêtre, France. Electronic address:

Objectives: The strategy of fertility preservation (FP) in cervical cancer has been challenged for several years and a therapeutic de-escalation seems to be necessary. In this context, we evaluated the oncological, fertility and obstetric outcomes of surgical techniques performed in our centre for FP.

Methods: This retrospective uni centric trial included 75 patients, managed at the Gustave Roussy Institute between 1995 and 2020, for cervical cancer (stage IB1 FIGO 2018) and having conducted a fertility preservation project after a complete pre-therapy work-up. The objective of this study was to understand our results on fertility and obstetrical outcomes and to correlate them with oncological data and finally to evaluate the evolution of our surgical practices.

Results: 54 patients benefited from an extended trachelectomy and no lymph node involvement was found. 1 patient received a complementary treatment postoperatively which did not allow to preserve her fertility. The recurrence rate was 4.8% (4/75) with one death described. 31 pregnancies were obtained, representing a pregnancy rate of 50%. 74% of pregnancies were obtained spontaneously and 60% of pregnancies were carried to term.

Conclusion: Our results are similar to those in the literature. Despite a fertility preservation project, only half of the patients were able to achieve a pregnancy.
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http://dx.doi.org/10.1016/j.gofs.2021.09.001DOI Listing
January 2022

Impact of Vaginal Symptoms and Hormonal Replacement Therapy on Sexual Outcomes After Definitive Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer: Results from the EMBRACE-I Study.

Int J Radiat Oncol Biol Phys 2022 02 1;112(2):400-413. Epub 2021 Sep 1.

Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands; Department of Radiotherapy, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands.

Purpose: To evaluate patient-reported sexual outcomes after chemoradiation therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer in the observational, prospective, multicenter EMBRACE-I study.

Methods And Materials: Sexual outcomes were assessed prospectively with the European Organization for Research and Treatment of Cancer Qualify of Life Questionnaire (EORTC-QLQ-CX24) at baseline and follow-up. Crude incidence and prevalence rates of sexual activity, vaginal functioning problems (dryness, shortening, tightening, pain during intercourse), and sexual enjoyment were evaluated. Associations between pain during intercourse and vaginal functioning problems or sexual enjoyment were calculated, pooling observations over all follow-ups (Spearman correlation coefficient). In patients who were frequently sexually active (≥50% of follow-ups), the effects of regular hormonal replacement therapy (HRT) on vaginal functioning problems were evaluated (Pearson χ).

Results: The analysis involved 1045 patients with a median follow-up of 50 months. Sexual activity was reported by 22% of patients at baseline and by 40% to 47% of patients during follow-up (prevalence rates). Vaginal functioning problems in follow-up were dryness (18%-21%), shortening (15%-22%), tightening (16%-22%), pain during intercourse (9%-21%), and compromised enjoyment (37%-47%). Pain during intercourse was significantly associated with vaginal tightening (r = 0.544), shortening (r = 0.532), and dryness (r = 0.408) and negatively correlated with sexual enjoyment (r = -0.407). Regular HRT was associated with significantly less vaginal dryness (P = .015), shortening (P = .024), pain during intercourse (P = .003), and borderline higher sexual enjoyment (P = .062).

Conclusions: Vaginal functioning problems are associated with pain and compromised sexual enjoyment. Further effort is required for the primary prevention of vaginal morbidity with dose optimization and adaptation. Secondary prevention strategies, including HRT for vaginal and sexual health after radiation therapy in locally advanced cervical cancer, should be considered and sexual rehabilitation programs should be developed further.
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http://dx.doi.org/10.1016/j.ijrobp.2021.08.036DOI Listing
February 2022

PAX3-NCOA1 alveolar rhabdomyosarcoma of the tongue: A rare entity with challenging diagnosis and management.

Pediatr Blood Cancer 2021 11 23;68(11):e29288. Epub 2021 Aug 23.

Department of Pediatric and Adolescent Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.

Alveolar rhabdomyosarcoma (ARMS) is associated with PAX3/PAX7-FOXO1 fusion, which confers specific clinic and biologic characteristics with inferior outcomes. A minority of tumors still histologically classified as "true" ARMS lack the canonical PAX-FOXO1 fusion but have new molecular alterations. We present the first case of PAX3-NCOA1 ARMS with clinical data and follow-up in a two-year-old girl with ARMS of the tongue and nodal extension, treated with chemotherapy, hemi glossectomy, lymph node dissection, and brachytherapy to conserve oral function and limit long-term sequelae. Given the rarity of such variant fusion in ARMS, international collaboration is required to evaluate its prognostic value.
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http://dx.doi.org/10.1002/pbc.29288DOI Listing
November 2021

Exclusive 3D-brachytherapy as a good option for stage-I inoperable endometrial cancer: a retrospective analysis in the gynaecological cancer GEC-ESTRO Working Group.

Clin Transl Oncol 2022 Feb 16;24(2):254-265. Epub 2021 Jul 16.

Radiation Oncology Department, University Hospital Leuven, Herestraat 49, 3000, Leuven, Belgium.

Purpose: Analyse outcomes of stage-I inoperable endometrial cancer (EC) patients from seven European centres treated with 3D-image-guided brachytherapy (IGBT) alone.

Materials And Methods: From 2004 to 2018, 62 patients (41 stage-IA and 21 IB) were retrospectively studied, analysing anaesthetic procedure, applicator type, BT-planning imaging, clinical target volume (CTV), BT schedule, overall daily-dose equivalent to 2 Gy (EQD2) to the CTV and D2 cm for organs at risk. Complications were evaluated using CTCAEv4 scores. The 2 and 5 year survival was calculated [cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS)]. Descriptive analysis and the Kaplan-Meier method were used for survival analysis.

Results: Mean follow-up: 32.8 months (SD 33.7). Spinal anaesthesia (38/62) followed by none (16/62) were the most common. Y-shaped Rotte applicators were used in 74% of patients. High-dose rate brachytherapy was administered in 89%. Median D90 to the CTV was 58.9 Gy (8.66-144 Gy). Eight patients presented relapse: four uterine, four nodal and four distant. The 2 and 5 year CSS was 93.3 and 80.5%, DFS 84.8 and 80.5%, LRFS was 93.1 and 88.7%, LRRFS was 91 and 91% and DMFS was 90.2 and 90.2%, respectively, CSS was better in stage-IA vs. IB (p = 0.043). Late vaginal and bladder G3-complication rates were 2.1%, respectively.

Conclusion: Inoperable EC patients can be safely treated by BT with 2 and 5 year CSS of 93 and 80.5%, respectively, with even better results for IA cases. Prospective studies on 3D-IGBT are necessary to better analyse EC patient outcomes based on dose and treated volumes.
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http://dx.doi.org/10.1007/s12094-021-02680-zDOI Listing
February 2022

Metabolic features of cancer cells impact immunosurveillance.

J Immunother Cancer 2021 06;9(6)

Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, INSERM, Paris, France

Background: Tumors rewire their metabolism to achieve robust anabolism and resistance against therapeutic interventions like cisplatin treatment. For example, a prolonged exposure to cisplatin causes downregulation of pyridoxal kinase (PDXK), the enzyme that generates the active vitamin B6, and upregulation of poly ADP-ribose (PAR) polymerase-1 (PARP1) activity that requires a supply of nicotinamide (vitamin B3) adenine dinucleotide. We investigated the impact of the levels of PDXK and PAR on the local immunosurveillance (ie, density of the antigen presenting cells and adaptive immune response by CD8 T lymphocytes) in two different tumor types.

Methods: Tumors from patients with locally advanced cervical carcinoma (LACC) and non-small cell lung cancer (NSCLC) were stained for PAR, PDXK, dendritic cell lysosomal associated membrane glycoprotein (DC-LAMP) and CD8 T cell infiltration. Their correlations and prognostic impact were assessed. Cisplatin-resistant NSCLC cell clones isolated from Lewis-lung cancer (LLC) cells were evaluated for PAR levels by immunoblot. Parental (PAR) and cisplatin-resistant (PAR) clones were subcutaneously injected into the flank of C57BL/6 mice. Tumors were harvested to evaluate their immune infiltration by flow cytometry.

Results: The infiltration of tumors by CD8 T and DC-LAMP cells was associated with a favorable overall survival in patients with LACC (p=0.006 and p=0.008, respectively) and NSCLC (p<0.001 for both CD8 T and DC-LAMP cells). We observed a positive correlation between PDXK expression and the infiltration by DC-LAMP (R=0.44, p=0.02 in LACC, R=0.14, p=0.057 in NSCLC), and a negative correlation between PAR levels and CD8 T lymphocytes (R=-0.39, p=0.034 in LACC, R=-0.18, p=0.017 in NSCLC). PARP1 is constitutively hyperactivated in cisplatin-resistant LLC cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PAR). Tumors formed by such cancer cells injected into immunocompetent mice were scarcely infiltrated by CD8 T (p=0.028) and antigen presenting cells (p=0.086).

Conclusions: Oncometabolic features can impact local immunosurveillance, providing new functional links between cisplatin resistance and therapeutic failure.
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http://dx.doi.org/10.1136/jitc-2021-002362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231002PMC
June 2021

Pulse-dose-rate interstitial brachytherapy in anal squamous cell carcinoma: clinical outcomes and patients' health quality perception.

J Contemp Brachytherapy 2021 Jun 18;13(3):263-272. Epub 2021 May 18.

Brachytherapy Unit, Radiation Oncology Department, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France.

Purpose: To examine clinical outcomes and quality of life of patients with anal squamous cell carcinoma treated with interstitial pulsed-dose-rate brachytherapy (PDR-BT) with a boost to residual tumor after external radiotherapy.

Material And Methods: Medical records of patients receiving a brachytherapy boost after radiotherapy for anal squamous cell carcinoma in our Institute between 2008 and 2019 were retrospectively reviewed. After receiving pelvic irradiation ± concurrent chemotherapy, patients received PDR-BT boost to residual tumor, in order to deliver a minimal total dose of 60 Gy. Patients' outcomes were analyzed, with primary focus on local control, sphincter preservation, morbidity, and quality of life.

Results: A total of 42 patients were identified, included 24, 13, and 5 patients with I, II, and III tumor stages, respectively. Median brachytherapy (BT) dose was 20 Gy (range, 10-30 Gy). Median dose per pulse was 42 cGy (range, 37.5-50 cGy). With median follow-up of 60.4 months (range, 5.4-127.4 months), estimated local control and colostomy-free survival rates at 5 years were both 88.7% (95% CI: 67.4-96.4%). The largest axis of residual lesion after external beam radiation therapy (EBRT) and poor tumor shrinkage were associated with more frequent relapses ( = 0.02 and = 0.007, respectively). Out of 40 patients with more than 6 months follow-up, only one experienced severe delayed toxicity (fecal incontinence). Health quality perception was very good or good in 20 of 22 (91%) patients, according to their replies of quality-of-life surveys. A total dose ≥ 63 Gy was associated with higher number of anorectal grade 1+ toxicities ( = 1.5 vs. = 0.61, = 0.02).

Conclusions: In this cohort of 42 patients with mainly I and II tumor stages, PDR-BT boost allowed for local control in 88.7% of patients, with only one grade 3 anorectal toxicity.
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http://dx.doi.org/10.5114/jcb.2021.106247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170522PMC
June 2021

COVID-19-Associated Pneumonia: Radiobiological Insights.

Front Pharmacol 2021 25;12:640040. Epub 2021 May 25.

Department of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, Brétigny-sur-Orge, France.

The evolution of SARS-CoV-2 pneumonia to acute respiratory distress syndrome is linked to a virus-induced "cytokine storm", associated with systemic inflammation, coagulopathies, endothelial damage, thrombo-inflammation, immune system deregulation and disruption of angiotensin converting enzyme signaling pathways. To date, the most promising therapeutic approaches in COVID-19 pandemic are linked to the development of vaccines. However, the fight against COVID-19 pandemic in the short and mid-term cannot only rely on vaccines strategies, in particular given the growing proportion of more contagious and more lethal variants among exposed population (the English, South African and Brazilian variants). As long as collective immunity is still not acquired, some patients will have severe forms of the disease. Therapeutic perspectives also rely on the implementation of strategies for the prevention of secondary complications resulting from vascular endothelial damage and from immune system deregulation, which contributes to acute respiratory distress and potentially to long term irreversible tissue damage. While the anti-inflammatory effects of low dose irradiation have been exploited for a long time in the clinics, few recent physiopathological and experimental data suggested the possibility to modulate the inflammatory storm related to COVID-19 pulmonary infection by exposing patients to ionizing radiation at very low doses. Despite level of evidence is only preliminary, these preclinical findings open therapeutic perspectives and are discussed in this article.
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http://dx.doi.org/10.3389/fphar.2021.640040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185272PMC
May 2021

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

J Contemp Brachytherapy 2021 Feb 18;13(1):24-31. Epub 2021 Feb 18.

Radiation Therapy Department, Gustave Roussy, Villejuif, France.

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 EQD2 D 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 EQD2 D was superior in the plan using oblique needles, with a median difference of 6.5 Gy (range, 1.7-8.5 Gy). Median D 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), = 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: Venezia applicator permits reproducible application to increase CTV coverage in patients with distal parametrial tumor residue during brachytherapy, while maintaining acceptable dose to OARs.
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http://dx.doi.org/10.5114/jcb.2021.103583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117708PMC
February 2021
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