Concurrent chemoradiotherapy (CRT) with blockade of the PD-1 pathway may enhance immune-mediated tumor control through increased phagocytosis, cell death, and antigen presentation. The NiCOL phase 1 ...trial (NCT03298893) is designed to determine the safety/tolerance profile and the recommended phase-II dose of nivolumab with and following concurrent CRT in 16 women with locally advanced cervical cancer. Secondary endpoints include objective response rate (ORR), progression free survival (PFS), disease free survival, and immune correlates of response. Three patients experience grade 3 dose-limiting toxicities. The pre-specified endpoints are met, and overall response rate is 93.8% 95%CI: 69.8-99.8% with a 2-year PFS of 75% 95% CI: 56.5-99.5%. Compared to patients with progressive disease (PD), progression-free (PF) subjects show a brisker stromal immune infiltrate, higher proximity of tumor-infiltrating CD3
T cells to PD-L1
tumor cells and of FOXP3
T cells to proliferating CD11c
myeloid cells. PF show higher baseline levels of PD-1 and ICOS-L on tumor-infiltrating EMRA CD4
T cells and tumor-associated macrophages, respectively; PD instead, display enhanced PD-L1 expression on TAMs, higher peripheral frequencies of proliferating Tregs at baseline and higher PD-1 levels at week 6 post-treatment initiation on CD4 and CD8 T cell subsets. Concomitant nivolumab plus definitive CRT is safe and associated with encouraging PFS rates. Further validation in the subset of locally advanced cervical cancer displaying pre-existing, adaptive immune activation is warranted.
Acquired perineal hernia is a rare complication following extensive pelvic surgery. Radiotherapy is also a predisposing factor. Perineal hernia can cause chronic perineal pain, bowel obstruction, ...urinary disorders and a cosmetically disfiguring defect. The treatment of perineal hernia is surgical, usually consisting of mesh repair via an abdominal or perineal approach.
We present a case report and a surgical video of a 42-year-old woman with history of a squamous cell carcinoma. This patient had 3 recurrences since the diagnosis and a symptomatic perineal hernia. Complete regression of the recurrent malignancy allowed us to treat the perineal hernia. We performed laparoscopic repair with prosthetic mesh in this patient who had undergone multiple surgeries and radiotherapy, while preserving the omental flap that was used to reconstruct the posterior part of the vagina.
There is no consensus concerning the preferred surgical approach, perineal or laparoscopic, as no study has demonstrated the superiority of either of these approaches. Laparoscopic repair for an acquired perineal hernia is safe and feasible. However, further studies including randomized trials are required to precisely evaluate the best surgical approach and type of mesh.
Most endocervical adenocarcinomas are human papillomavirus (HPV)-related cancers associated with p16 immunostaining. Ovarian metastasis from cervical cancer is a rare phenomenon, the mechanism of ...dissemination remains unclear. The diagnosis of metastasis may be difficult to establish when the ovarian neoplasm presents features consistent with primary tumor. Immunohistochemical expression of p16 in ovarian tumors can guide the diagnosis of metastasis from HPV-related cervical cancer, but p16 positivity is nonspecific. Identical HPV genotype in the paired endocervical and ovarian tumors is a better marker for cervical origin, which may also be confirmed by identical HPV integration site.
Two women presented with HPV18 cervical adenocarcinoma. No signs of disease were visible on MRI after treatment. After several years of follow-up, mucinous ovarian tumors were discovered in both patients. Molecular analyses showed that the ovarian lesions were HPV18-positive; indicating a primary cervical origin. A third woman was diagnosed with grade 1 ovarian endometrioid carcinoma with no peritoneal carcinomatosis. Final histological examination and HPV genotyping revealed HPV18-related in situ endometrioid adenocarcinoma in the endocervix and HPV18-related invasive endometrioid adenocarcinoma in the endometrium and both ovaries. Additional molecular analyses performed in two patients identified the same HPV integration sites in both the ovarian and cervical tumors, confirming that the ovarian mass was a metastasis from the cervical adenocarcinoma.
We report three new cases of ovarian neoplasia in which the diagnosis of metastasis from cervical cancer was supported by the same HPV genotype and the same integration site in the paired cervical and ovarian tumors. To our knowledge, this is the first report of molecular evidence of the cervical origin of an ovarian metastasis. HPV screening should be performed in ovarian tumors for all patients with history of cervical neoplasia.
Breast cancer (BC) remains one of the most commonly diagnosed malignancies in women. There is increasing interest in the development of non-invasive screening methods. Volatile organic compounds ...(VOCs) emitted through the metabolism of cancer cells are possible novel cancer biomarkers. This study aims to identify the existence of BC-specific VOCs in the sweat of BC patients. Sweat samples from the breast and hand area were collected from 21 BC participants before and after breast tumor ablation. Thermal desorption coupled with two-dimensional gas chromatography and mass spectrometry was used to analyze VOCs. A total of 761 volatiles from a homemade human odor library were screened on each chromatogram. From those 761 VOCs, a minimum of 77 VOCs were detected within the BC samples. Principal component analysis showed that VOCs differ between the pre- and post-surgery status of the BC patients. The Tree-based Pipeline Optimization Tool identified logistic regression as the best-performing machine learning model. Logistic regression modeling identified VOCs that distinguish the pre-and post-surgery state in BC patients on both the breast and hand area with sensitivities close to 1. Further, Shapley additive explanations and the probe variable method identified the most important and pertinent VOCs distinguishing pre- and post-operative status which are mostly of distinct origin for the hand and breast region. Results suggest the possibility to identify endogenous metabolites linked to BC, hence proposing this innovative pipeline as a stepstone to discovering potential BC biomarkers. Large-scale studies in a multi-centered VOC analysis setting must be carried out to validate obtained findings.
To assess the decrease in the number of bowel resections (BR) necessary to achieve complete cytoreduction (CC-0) in advanced epithelial ovarian cancer (EOC) permitted by neoadjuvant chemotherapy ...(NAC).
Patients were selected from a population of advanced EOC cases diagnosed between 2002 and 2009 at the Curie Institute: 97 patients with Federation International of Gynecology and Obstetrics IIIc and IV with unresectable disease treated with NAC followed by interval debulking surgery were included. We proceeded to a systematic blinded review of all the surgical reports pre-and post-NAC by two different surgeons to assess the surgical procedures required to obtain CC-0.
Before NAC, at least 84 patients (87%) would have required BR to obtain a CC-0 resection. At interval debulking surgery, 47 (49%) still required a BR, which corresponds to a decrease of 38% (p<0.0001). The same decrease was observed for resection of small bowel, colon and rectosigmoid, as follows: 54 to 17 (77% to 24%, p<0.0001), 45 to 19 (56% to 24%, p<0.0001) and 72 to 25 (90% to 31%, p<0.0001), respectively. The median overall survival (OS) among CC-0 patients with and without BR was 57 months 95% confidence interval (CI)=25-90 months and 50 months 95% CI=43-57 months, respectively (p=0.71). The OS among patients without complete resection was significantly worse, with a median of 21 months (95% CI=17-32 months, p<0.0001).
NAC significantly reduces the need and rate of BR in advanced EOC, but also of small bowel, colon and rectosigmoid resection. There is no loss of OS, after BR especially if the debulking surgery is complete.
Quality Indicators for ovarian cancer (OC) have been developed by the European Society of Gynaecological Oncology (ESGO) and by the French National Cancer Institute (Institut National du Cancer, ...INCa). The aim of the study was to characterize OC care distribution in France by case-volume and to prospectively evaluate the adherence of high-volume institutions to INCa/ESGO quality indicators.
The cost-utility of radical surgery in ovarian cancer (CURSOC) trial is a prospective, multicenter, comparative and non-randomized study that includes patients with stage IIIC-IV epithelial OC treated in nine French health care tertiary institutions. Adherence to institutional quality indicators were anonymously assessed by an independent committee. OC care distribution in France were provided by the nationwide database of hospital procedures.
More than half of patients are treated in low-volume institutions. Among the nine high-volume centers participating in the study, four (44.4%) met all institutional INCa/ESGO quality indicators. The other five (55.6%) did not fulfil one of the quality indicator criteria.
Access to high-volume OC providers in France is restricted to a minority of patients, and yet half of the referral institutions included in this study failed to meet all recommended institutional quality indicators. It is mandatory that national authorities work both to improve OC centralization and to incorporate quality assurance programs into certified centers.
The aim was to evaluate the impact of local surgery performed during the year after MBC diagnosis on patients' outcomes from a large reallife cohort.
Locoregional treatment for patients with MBC at ...the time of diagnosis remains debated.
Women with newly diagnosed, de novo stage IV MBC and who started MBC treatment between January 2008 and December 2014 in one of the 18 French Comprehensive Cancer Centers were included (NCT03275311). The impact of local surgery performed during the first year on overall survival (OS) and progression-free survival (PFS) was evaluated by the Cox proportional hazards model in a 12 month-landmark analysis.
Out of 16,703 patients in the ESME database, 1977 had stage IV MBC at diagnosis, were alive and progression-free at 12 months and eligible for this study. Among them, 530 (26.8%) had received primary breast cancer surgery within 12 months. A greater proportion of patients who received surgery had less than 3 metastatic sites than the no-surgery group (90.8% vs 78.2%, P < 0.0001). Surgery within 12 months was associated with treatment with chemotherapy, HER2-targeted therapy (89.1% vs 69.6%, P < 0.0001) and locoregional radiotherapy (81.7% vs 32.5%, P < 0.0001). Multivariable analyses showed that surgery performed within 12 months was associated with longer OS and PFS (adjusted HR 95%CI = 0.75 0.61-0.92 and 0.72 0.63-0.83, respectively), which were also affected by pattern and number of metastatic sites, histological subtype, and age.
In the large ESME cohort, surgery within 1 year after de novo MBC diagnosis was associated with a significantly better OS and PFS.
Description of fertility and prognosis of patients with borderline ovarian tumor (BOT) treated by fertility-sparing surgery through a longitudinal study from the French national cancer network.
All ...consecutive patients diagnosed with BOT from the French National Network dedicated to Ovarian Malignant Rare Tumors from 2010 and 2017 were selected. In 2018, an update was made by sending a questionnaire regarding recurrence and fertility to patients aged under 43 years at diagnosis and treated conservatively. We compared the characteristics of the patients with/without recurrence and with/without live birth.
Fifty-two patients aged 18 to 42 years presented a desire of pregnancy. Thirty patients (58%) presented a FIGO IA tumor, and 20 patients were treated by bilateral cystectomies (38%). We observed at least one live birth for 33 patients (63%) and local recurrences in 20 patients (38%). Both recurrence and live birth in 17 patients (33%) were reported, with recurrence occurring before pregnancy, after a second fertility-sparing treatment, in half of the cases. No factors associated with recurrence or live birth in this study were identified. Moreover, in this population, both recurrence and live birth were independent of age, with a linear risk along time. Disease-free survival was worse for patients treated with bilateral cystectomy (n = 20, 38%), with no difference in terms of fertility.
Two third of the patients experienced life birth after conservation surgery. We did not highlight an age/time from surgery for which the risk of recurrence outweighs the chance of pregnancy and to radicalize surgery. Moreover, almost a quarter of the live birth occurred after recurrence, with no more further event to date in these patients. The results encourage to consider a second fertility-sparing surgery after local borderline recurrence in the case of pregnancy desire. All these decisions must be discussed in specialized multidisciplinary boards.
•Conservative treatment of BOT is a safe procedure in terms of overall survival but increases the risk of local recurrence.•Pregnancy rate after conservative management of BOT is good, even after a second conservative surgery for local recurrence.•Risks of recurrence and pregnancy are linear along time, giving no argument to radicalize surgery after a specific follow-up.
Introduction
Improvement in overall survival (OS) by locoregional treatment (LRT) of the primary tumor in de novo metastatic breast cancer (MBC) patients remains controversial.
Objective
The aim of ...our study was to evaluate the impact of LRT on OS in a large retrospective cohort of de novo MBC patients, with regard to immunohistochemical characteristics and pattern of metastatic dissemination.
Methods
We conducted a multicentric retrospective study of patients diagnosed with de novo MBC selected from the French Epidemiological Strategy and Medical Economics MBC database (NCT03275311) between 2008 and 2014. Overall, 4276 women were included in the study. LRT comprised either radiotherapy, surgery, or both.
Results
LRT was used in 40% of patients. Compared with no LRT, patients who received LRT were younger (
p
< 0.0001) and were more likely to have only one metastatic site (
p
< 0.0001) or bone-only metastases (
p
< 0.0001). LRT was associated with a significantly better OS based on landmark multivariate analysis at 1-year (hazard ratio 0.65, 95% confidence interval 0.55–0.76,
p
< 0.001). Similar results were observed in all sensitivity analyses, including propensity score matching. In subgroup analysis, LRT was associated with better OS in patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (61.6 vs. 45.9 months,
p
< 0.001) and HER2-positive tumors (77.2 vs. 52.6 months,
p
= 0.008), but not in triple-negative tumors (19 vs. 18.6 months,
p
= 0.54), and was also associated with a reduction in the risk of death in visceral metastatic patients (
p
< 0.001).
Conclusions
LRT was associated with a significantly better OS in de novo MBC patients, including patients with visceral involvement at diagnosis; however, LRT did not impact OS in triple-negative MBC.
Abstract Aim The objective of this study was to determine the effects of axillary lymph node dissection (ALND) versus sentinel lymph node biopsy alone (SLNB) on the survival of patients with 3 or ...more metastatic lymph nodes (MLN) in invasive breast cancer. Methods Data of 9521 patients with invasive T1-2M0 breast carcinoma and initial treatment with SLNB completed or not by ALND and 3 or more MLN were extracted from the SEER database. Univariate and multivariate analyses were performed. Results Overall, 9521 patients were included in the study. SLNB-alone compared with ALND did not result in different overall survival (OS) or specific survival (SS) for patients with 3 or more MLN (p = 0.46 and 0.58, respectively). In subgroup analyses, OS was comparable between SLNB-alone and ALND when patients had only 3 or more than 3 MLN. When patients had 3 MLN, the 5-year SS was significantly better for patients with ALND compared with SLNB-alone: 91.5% and 85.1%, respectively (p = 0.02). The Hazard Ratio (HR) for OS comparing SLNB-alone with ALND adjusting for age, adjuvant radiotherapy, tumor size, estrogen receptor status, grade and tumor type resulted in an HR of 1.05 (95% CI, 0.72–1.54, p = 0.77). Conclusion In conclusion, patients with a T1–T2 invasive breast cancer and at least 3 MLN do not benefit from ALND after SLNB for specific and overall survival, thus limiting ALND to a staging procedure. A subgroup of patients with 3 MLN had a better SS with ALND, possibly due to an under-staging of the SLNB-alone group.
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