Radiation therapy of anal canal carcinoma

La radio(chimio)thérapie correspond au traitement de référence des carcinomes épidermoïdes du canal anal localisés qui représentent la majorité des cas. Elle a pour objectif d’obtenir une stérilisation tumorale définitive tout en conservant un sphincter anal fonctionnel. Cet article a pour objectif de préciser les indications et les modalités de la radiothérapie pelvienne dans cette situation. Il sera également question des nouvelles modalités d’irradiation (Radiothérapie Conformationnelle avec Modulation d’Intensité ; Tomothérapie hélicoïdale et irradiation avec modulation d’intensité volumétrique par Arc thérapie) qui permettent à la fois une meilleure définition des volumes cibles et une meilleure protection des organes à risque (intestin grêle, recto-sigmoïde, vessie, organes génitaux notamment). Cette dernière réduit la toxicité induite, ce qui permet d’envisager une réduction de la durée totale du traitement (réduction de la durée de la pause thérapeutique entre les 2 séquences de radiothérapie, voire suppression de cette pause avec traitement continu). La réduction de la toxicité devrait également permettre d’augmenter la dose totale délivrée dans le volume cible. L’intérêt d’une telle stratégie mérite d’être évalué.Radio(chemo)therapy is the standard treatment of localized epidermoid carcinomas of the anal canal, which represent the majority of cases. The aim of treatment is to obtain tumor sterilization while preserving functional anal sphincter. This article concerns the indications and the modalities of radiotherapy in this situation, with special attention to the new available radiation techniques (conformational static field intensity modulated radiotherapy; helicoidal tomotherapy; volumetric modulated arc therapy). These developments mainly allow to reduce the dose to normal tissues and organs at risk thereby minimizing the risk of toxicity. The reduction of the induced morbidity should allow to shorten the classical 2 to 6 weeks gap period between the two sequences of radiotherapy and therefore the total duration of treatment. It also should allow dose escalation to the tumor volume potentially leading to improved locoregional control

Postoperative treatment of intermediate-risk early stage cervical cancer: results of a survey from the Gynecology Study Group in the AIRO Gyn and MITO Groups

This survey investigated prognostic factors, treatment modalities, references followed and radiation oncologists' opinions to prescribe adjuvant therapy in early intermediate-risk cervical cancer. All but one recommended pelvic radiotherapy ± vaginal boost (45%) with or without chemotherapy (20%). 88% believed other prognostic factors could integrate classic risk criteria. 66% considered chemo-radiation indicated in case of lymphovascular invasion and suboptimal node dissection, high grade, size ≥ 4cm, non squamous histology and risk factors combination. This wide heterogeneity of treatments reflects the different guideline options due to the lack of defined indications. The need of integrating the classic prognostic factors with others factors was unanimously expressed by radiation oncologists. The best local and systemic therapy should be established through new studies. These results highlighted the need of a position paper to standardize adjuvant treatment in Italy and to design collaborative studies to clarify the controversial aspects

Recurrent Endometrial Cancer: Which Is the Best Treatment? Systematic Review of the Literature

Background: Endometrial cancer is the most common gynaecological tumour in developed countries. The overall rate of relapse has remained unchanged in recent decades. Recurrences occur in approximately 20% of endometrioid and 50% of non-endometrioid cases. The aim of this systematic review is to compare different therapeutic strategies in the treatment of endometrial cancer recurrence to evaluate their prognostic and curative effects based on site and type of recurrence. Methods: This systematic review of literature was conducted in accordance with the PRISMA guidelines. The study protocol was registered on PROSPERO (CRD42020154042). PubMed, Embase, Chocrane and Cinahl databases were searched from January 1995 to September 2021. Five retrospective studies were selected. Results: A total of 3571 studies were included in the initial search. Applying the screening criteria, 299 articles were considered eligible for full-text reading, of which, after applying the exclusion criteria, 4 studies were selected for the final analysis and included in the systematic review. No studies were included for a quantitative analysis. We divided the results according to the location of the recurrence: locoregional recurrence, abdominal recurrence and extra abdominal recurrence. Conclusion: the treatment of choice should be assessed according to the relapse location and to the presence of single or multiple lesions. A crucial role in the decision-making algorithm is also the type of adjuvant treatment received at the time of the first diagnosis

Circulating human papillomavirus DNA detected using droplet digital PCR in the serum of patients diagnosed with early stage human papillomavirus-associated invasive carcinoma

International audienceSpecific human papillomavirus genotypes are associated with most ano-genital carcinomas and a large subset of oro-pharyngeal carcinomas. Human papillomavirus DNA is thus a tumour marker that can be detected in the blood of patients for clinical monitoring. However, data concerning circulating human papillomavirus DNA in cervical cancer patients has provided little clinical value, due to insufficient sensitivity of the assays used for the detection of small sized tumours. Here we took advantage of the sensitive droplet digital PCR method to identify circulating human papillomavirus DNA in patients with human papillomavirus-associated carcinomas. A series of 70 serum specimens, taken at the time of diagnosis, between 2002 and 2013, were retrospectively analyzed in patients with human papillomavirus-16 or human papillomavirus-18-associated carcinomas, composed of 47 cases from the uterine cervix, 15 from the anal canal and 8 from the oro-pharynx. As negative controls, 18 serum samples from women with human papillomavirus-16-associated high-grade cervical intraepithelial neoplasia were also analyzed. Serum samples were stored at -80 degrees C (27 cases) or at -20 degrees C (43 cases). DNA was isolated from 200 mu l of serum or plasma and droplet digital PCR was performed using human papillomavirus-16 E7 and human papillomavirus-18 E7 specific primers. Circulating human papillomavirus DNA was detected in 61/70 (87%) serum samples from patients with carcinoma and in no serum from patients with cervical intraepithelial neoplasia. The positivity rate increased to 93% when using only serum stored at -80 degrees C. Importantly, the two patients with microinvasive carcinomas in this series were positive. Quantitative evaluation showed that circulating viral DNA levels in cervical cancer patients were related to the clinical stage and tumour size, ranging from 55 +/- 85 copies/ml (stage I) to 1774 +/- 3676 copies/ml (stage IV). Circulating human papillomavirus DNA is present in patients with human papillomavirus-associated invasive cancers even at sub-clinical stages and its level is related to tumour dynamics. Droplet digital PCR is a promising method for circulating human papillomavirus DNA detection and quantification. No positivity was found in patients with human papillomavirus-associated high grade cervical intraepithelial neoplasia

Recurrent Endometrial Cancer: Which Is the Best Treatment? Systematic Review of the Literature

Simple Summary Endometrial cancer is the most common gynaecological tumour in developed countries. The aim of this systematic review is to compare different therapeutic strategies in the treatment of endometrial cancer recurrence to evaluate their prognostic and curative effects. The treatment of choice should be assessed according to the relapse location and to the presence of single or multiple lesions. A crucial role is also played by the type of adjuvant treatment received at the time of the first diagnosis. The molecular pattern will also be investigated in future studies. This will make it possible to personalise treatments. Background: Endometrial cancer is the most common gynaecological tumour in developed countries. The overall rate of relapse has remained unchanged in recent decades. Recurrences occur in approximately 20% of endometrioid and 50% of non-endometrioid cases. The aim of this systematic review is to compare different therapeutic strategies in the treatment of endometrial cancer recurrence to evaluate their prognostic and curative effects based on site and type of recurrence. Methods: This systematic review of literature was conducted in accordance with the PRISMA guidelines. The study protocol was registered on PROSPERO (CRD42020154042). PubMed, Embase, Chocrane and Cinahl databases were searched from January 1995 to September 2021. Five retrospective studies were selected. Results: A total of 3571 studies were included in the initial search. Applying the screening criteria, 299 articles were considered eligible for full-text reading, of which, after applying the exclusion criteria, 4 studies were selected for the final analysis and included in the systematic review. No studies were included for a quantitative analysis. We divided the results according to the location of the recurrence: locoregional recurrence, abdominal recurrence and extra abdominal recurrence. Conclusion: the treatment of choice should be assessed according to the relapse location and to the presence of single or multiple lesions. A crucial role in the decision-making algorithm is also the type of adjuvant treatment received at the time of the first diagnosis

Genetic profiles of cervical tumors by high‐throughput sequencing for personalized medical care

International audienceCancer treatment is facing major evolution since the advent of targeted therapies. Building genetic profiles could predict sensitivity or resistance to these therapies and highlight disease-specific abnormalities, supporting personalized patient care. In the context of biomedical research and clinical diagnosis, our laboratory has developed an oncogenic panel comprised of 226 genes and a dedicated bioinformatic pipeline to explore somatic mutations in cervical carcinomas, using high-throughput sequencing. Twenty-nine tumors were sequenced for exons within 226 genes. The automated pipeline used includes a database and a filtration system dedicated to identifying mutations of interest and excluding false positive and germline mutations. One-hundred and seventy-six total mutational events were found among the 29 tumors. Our cervical tumor mutational landscape shows that most mutations are found in PIK3CA (E545K, E542K) and KRAS (G12D, G13D) and others in FBXW7 (R465C, R505G, R479Q). Mutations have also been found in ALK (V1149L, A1266T) and EGFR (T259M). These results showed that 48% of patients display at least one deleterious mutation in genes that have been already targeted by the Food and Drug Administration approved therapies. Considering deleterious mutations, 59% of patients could be eligible for clinical trials. Sequencing hundreds of genes in a clinical context has become feasible, in terms of time and cost. In the near future, such an analysis could be a part of a battery of examinations along the diagnosis and treatment of cancer, helping to detect sensitivity or resistance to targeted therapies and allow advancements towards personalized oncology

Genetic profiles of cervical tumors by high-throughput sequencing for personalized medical care

International audienceCancer treatment is facing major evolution since the advent of targeted therapies. Building genetic profiles could predict sensitivity or resistance to these therapies and highlight disease-specific abnormalities, supporting personalized patient care. In the context of biomedical research and clinical diagnosis, our laboratory has developed an oncogenic panel comprised of 226 genes and a dedicated bioinformatic pipeline to explore somatic mutations in cervical carcinomas, using high-throughput sequencing. Twenty-nine tumors were sequenced for exons within 226 genes. The automated pipeline used includes a database and a filtration system dedicated to identifying mutations of interest and excluding false positive and germline mutations. One-hundred and seventy-six total mutational events were found among the 29 tumors. Our cervical tumor mutational landscape shows that most mutations are found in PIK3CA (E545K, E542K) and KRAS (G12D, G13D) and others in FBXW7 (R465C, R505G, R479Q). Mutations have also been found in ALK (V1149L, A1266T) and EGFR (T259M). These results showed that 48% of patients display at least one deleterious mutation in genes that have been already targeted by the Food and Drug Administration approved therapies. Considering deleterious mutations, 59% of patients could be eligible for clinical trials. Sequencing hundreds of genes in a clinical context has become feasible, in terms of time and cost. In the near future, such an analysis could be a part of a battery of examinations along the diagnosis and treatment of cancer, helping to detect sensitivity or resistance to targeted therapies and allow advancements towards personalized oncology

Cervical cancer patterns of care in Italy: A radiation oncology survey of MITO and AIRO GYN groups

Large heterogeneity in therapeutic approaches to cervical cancer (CC) patients has been registered worldwide; a national survey exploring practice settings and equipments in CC treatment was distributed to radiation oncologists. Questionnaires were compiled in 90 of 194 Centers (compliance: 46.3 %). Most of respondents reported the presence of multidisciplinary tumor board, and modern equipments/techniques; 55.5 % of centers reported >1 brachytherapy (BT) equipment, thus implying the need to refer their patients outside for the remaining centers. Post-surgery radiotherapy was performed in 96.7 % of early CC (ECC) cases with pathological high risk factors. Exclusive chemoradiation with concomitant platinum schedules was referred to be used by 84.4 % of centers in locally advanced CC. Alternative options were reported with a range between 4.4 and 28.9 %. The present survey reports a broad spectrum of therapeutic options for CC in Italy. Availability and use of modern techniques is quite diffuse, but the distribution of BT resources and skills remains a challenge

Neoadjuvant Chemoradiotherapy With Simultaneous Integrated Boost in Locally Advanced Cervical Cancer: Long Term Results of a Single-Center Experience

Aim of this study was to analyze the efficacy and tolerability of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) associated with cisplatin-based chemotherapy in preoperative setting of patients with locally advanced cervical cancer (LACC). From June 2013 to September 2019, we analyzed patients with LACC who had undergone neoadjuvant chemoradiation (CRT). A radiation dose of 39.6 Gy, 1.8 Gy/fraction was delivered to the pelvis plus a radiation dose to the primary tumor delivered with SIB-VMAT strategy for a total of 50.6Gy, 2.3Gy/fraction in 25 fractions. Cisplatin-based chemotherapy was delivered combined with radiotherapy. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 7 to 8 weeks from CRT. One hundred forty-eight patients (median age: 49.5 years; FIGO stage IB2: 7, IIA: 8, IIB: 106, IIIA: 5; IIIB: 16; IVA: 5, IVB: 1; N0: 56, N1: 92) were analyzed. The treatment was well tolerated with good compliance: no grade 3/4 gastrointestinal or genitourinary toxicity was reported; grade 3 neutropenia was described in five cases. Pathological complete response (pCR) was documented in 68 cases (46%) and 32 patients (21.6%) had microscopic residual disease. Pathological nodal involvement was observed in 23 patients (15.5%). At median follow-up of 59 months (range: 27-100), the 3-year local control was 78.5%, whereas the 3-year metastasis-free survival was 70.5%. The 3-year overall survival rate was 89.0%. Neoadjuvant CRT with SIB-VMAT followed by radical surgery results in a high rate of pathologically assessed complete response and a very encouraging local control rate, with acceptable toxicity

EFFICACY AND SAFETY OF STEREOTACTIC BODY RADIOTHERAPY (SBRT) IN OLIGOMETASTATIC UTERINE CANCER (MITO-RT2/RAD STUDY): A LARGE, REAL-WORLD STUDY IN COLLABORATION WITH AIRO GYN, MITO and MaNGO Groups

Objective: This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of oligometastatic/persistent/recurrent uterine cancer patients. Methods: Clinical and radiotherapy data from several radiotherapy centers treating patients by stereotactic body radiotherapy between March 2006 and October 2021 were collected. Objective response rate was defined as complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. Primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2-year actuarial local control rate 'per-lesion' basis. Secondary endpoints were progression-free survival and overall survival, as well as toxicity. Results: 157 oligometastatic/persistent/recurrent uterine cancer patients bearing 272 lesions treated by stereotactic body radiotherapy at 14 centers were analyzed. Lymph node metastases (137, 50.4%) were prevalent, followed by parenchyma lesions (135, 49.6%). Median total dose was 35 Gy (10-75.2), in five fractions (range 1-10). Complete and partial responses were 174 (64.0%), and 54 (19.9%), respectively. Stable disease was registered in 29 (10.6%), while 15 (5.5%) lesions progressed. Type of lesion (lymph node), volume (≤ 13.7 cc) and total dose (BED10 >59.5 Gy) were significantly associated with a higher probability of achieving complete response. Patients achieving complete response (CR) 'per-lesion' basis experienced a 2-year actuarial local control rate of 92.4% versus 33.5% in lesions not achieving complete response (NCR) (p<0.001). Moreover, the 2-year actuarial progression-free survival rate in patients with CR was 45.4%, while patients with NCR had a 2-year rate of 17.6% (p value: <0.001). Finally, patients who had a CR had a 2-year overall survival rate of 82.7%, compared to 56.5% for NCR ONES (P VALUE: <0.001) . Severe acute toxicity was around 2%, including one toxic death due to gastric perforation, and severe late toxicity around 4%. Conclusion: The efficacy of stereotactic body radiotherapy in this setting was confirmed. The low toxicity profile and the high local control rate in complete responder patients encourage the wider use of this approach