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BACKGROUND: Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated with poorer survival outcomes compared with no residual disease. We performed a meta-analysis to assess the impact of varying levels of residual disease status on survival outcomes in patients with ovarian cancer who have undergone primary cytoreductive surgery or interval cytoreductive surgery in the setting of new therapies for this disease. METHODS: Medline, Embase, and Cochrane databases (January 2011 - July 2020) and grey literature, bibliographic and key conference proceedings, were searched for eligible studies. Fixed and random-effects meta-analyses compared progression and survival by residual disease level across studies. Heterogeneity between comparisons was explored via type of surgery, disease stage, and type of adjuvant chemotherapy. RESULTS: Of 2832 database and 16 supplementary search articles screened, 50 studies were selected; most were observational studies. The meta-analysis showed that median progression-free survival and overall survival decreased progressively with increasing residual disease (residual disease categories of 0 cm, > 0-1 cm and > 1 cm). Compared with no residual disease, hazard ratios (HR) for disease progression increased with increasing residual disease category (1.75 [95% confidence interval: 1.42, 2.16] for residual disease > 0-1 cm and 2.14 [1.34, 3.39] for residual disease > 1 cm), and also for reduced survival (HR versus no residual disease, 1.75 [ 1.62, 1.90] for residual disease > 0-1 cm and 2.32 [1.97, 2.72] for residual disease > 1 cm). All comparisons were significant (p

Background: Cervical cancer often originates from cervical cell dysplasia. Previous studies mainly focused on surgical margins and high-risk human papillomavirus persistence as factors predicting recurrence. New research highlights the significance of positive findings from endocervical curettage (ECC) during excision treatment. However, the combined influence of surgical margin and ECC status on dysplasia recurrence risk has not been investigated. Methods: In this retrospective study, data from 404 women with high-grade squamous intraepithelial lesions (HSIL) who underwent large loop excision of the transformation zone (LLETZ) were analyzed. Records were obtained retrospectively from the hospital's patient database including information about histopathological finding from ECC, endocervical margin status with orientation of residual disease after LLETZ, recurrent/persistent dysplasia after surgical treatment and need for repeated surgery (LLETZ or hysterectomy). Results: Patients with cranial (= endocervical) R1-resection together with cells of HSIL in the ECC experienced re-surgery 17 times. With statistical normal distribution, this would have been expected to happen 5 times (p < 0.001). The Fisher's exact test confirmed a statistically significant connection between the resection status together with the result of the ECC and the reoccurrence of dysplasia after surgery (p < 0,001). 40,6% of the patients with re-dysplasia after primary LLETZ had shown cranial R1-resection together with cells of HSIL in the ECC. Investigating the risk for a future abnormal Pap smear, patients with cranial R1-resection together with dysplastic cells in the ECC showed the greatest deviation of statistical normal distribution with SR = 2.6. Conclusion: Our results demonstrate that the future risk of re-dysplasia, re-surgery, and abnormal Pap smear for patients after LLETZ due to HSIL is highest within patients who were diagnosed with cranial (endocervical) R1-resection and with cells of HSIL in the ECC in their primary LLETZ. Consequently, the identification of patients, who could benefit of intensified observation or required intervention could be improved. [ABSTRACT FROM AUTHOR]

Purpose: Ischemic complications after nipple-sparing mastectomy (NSM) can be ameliorated by 2-stage procedures wherein devascularization of the nipple-areolar complex (NAC) and lumpectomy with or without nodal staging surgery is performed first (1S), weeks prior to a completion NSM (2S). We report the time interval between procedures in relation to the presence of residual carcinoma at 2S NSM. Methods: Women with breast cancer who received 2S NSM from 2015 to 2022 were identified. Both patient level and breast level analyses were conducted. Clinical staging at presentation, pathologic staging at 1S and residual disease at 2S pathology are noted. Residual disease was classified as microscopic (1–2 mm), minimal (3–10 mm), and moderate (> 10 mm). Results: 59 patients (108 breasts) underwent 2S NSM. The median time interval between 1 and 2S for all patients was 34 days: 31 days for upfront surgery invasive cancer, 41 days for upfront DCIS surgery and 31 days for those receiving neoadjuvant therapy. Completion NSM was performed within 6 weeks for 72% of the breasts analyzed. Of the 53 breasts with invasive cancer on 1S pathology, 35% (19/53) had no residual invasive disease and 24.5% (13/53) had neither residual invasive nor in situ carcinoma on final 2S. Among the 50 women who had upfront surgery, 16 (32%) had residual invasive cancer found at 2S NSM, 9 of which had less than or equal to 1 cm disease. Conclusion: Invasive cancers were completely resected during 1S procedure in 65% of breasts. Residual disease was minimal and there was only one case of upstaging at 2S. Added time of two-stage surgery is offset by a reduction in ischemic mastectomy flap complications. [ABSTRACT FROM AUTHOR]

Purpose: For operable triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), clinical prognostication and postoperative decision-making relies exclusively on whether a pathologic complete response (pCR) is achieved or not. We evaluated whether extent of disease at presentation further influenced overall survival (OS) among patients with pCR or with residual disease (RD) following NAC. Methods: Patients with stage I–III TNBC who underwent NAC were identified from the National Cancer Database from 2010 to 2019. Overall survival was assessed by disease extent using the Kaplan–Meier method and Cox proportional hazards regression for univariate and multivariable analysis. Results: A total of 35,598 patients met inclusion criteria, and 11,967 achieved pCR. Ten-year OS was 88.5% and varied by cT and cN category at presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (90.9%) and was worst in those with cT3-4, cN2-3 disease (72.0%). A total of 23,631 patients had RD. Ten-year OS was 60.1% and varied by cT and cN category at presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (73.0%) and was worst in those with cT3-4, cN2-3 disease (36.3%). Notably, OS was significantly poorer for patients with cT3-4, cN2-3 disease at diagnosis and pCR versus those with cT1-2 cN0 and RD (aHR 1.30, 95% confidence interval 1.03–1.63, p = 0.03). Conclusions: Among patients with TNBC, extent of disease at presentation was prognostic for OS independently of response to NAC. Patients with advanced stage at presentation had poorer OS even in the context of pCR. Further investigation is needed to evaluate whether additional adjuvant therapy strategies should be considered for these patients. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008–2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; ≤21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0–21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC ≤21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0–21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS. • Time to chemotherapy after PDS for advanced EOC does not influence 5-year survival. • Time to chemotherapy is associated with 2-year survival in patients with no residual disease (R0) after PDS. • Time to chemotherapy >42 days is associated with excess mortality in patients with FIGO stage IV and R0 after PDS. • Time to chemotherapy is not associated with survival in patients with advanced EOC and residual disease after PDS. [ABSTRACT FROM AUTHOR]

Abstract Background Cervical cancer often originates from cervical cell dysplasia. Previous studies mainly focused on surgical margins and high-risk human papillomavirus persistence as factors predicting recurrence. New research highlights the significance of positive findings from endocervical curettage (ECC) during excision treatment. However, the combined influence of surgical margin and ECC status on dysplasia recurrence risk has not been investigated. Methods In this retrospective study, data from 404 women with high-grade squamous intraepithelial lesions (HSIL) who underwent large loop excision of the transformation zone (LLETZ) were analyzed. Records were obtained retrospectively from the hospital’s patient database including information about histopathological finding from ECC, endocervical margin status with orientation of residual disease after LLETZ, recurrent/persistent dysplasia after surgical treatment and need for repeated surgery (LLETZ or hysterectomy). Results Patients with cranial (= endocervical) R1-resection together with cells of HSIL in the ECC experienced re-surgery 17 times. With statistical normal distribution, this would have been expected to happen 5 times (p

To determine the predictive factors for residual disease occurring after surgical removal of congenital cholesteatomas and whether these predictive factors differ between microscopic ear surgery (MES) using data from the literature and transcanal endoscopic ear surgery (TEES) using data from our own institution. Twenty-three patients with a congenital cholesteatoma who underwent surgical treatment at Yamagata University Hospital between December 2011 and December 2017 were retrospectively investigated. We divide TEES into three different approaches: non-powered TEES, powered TEES and dual MES/TEES. Main outcome measures were Potsic stage, closed or open congenital cholesteatoma type, TEES surgical approach, appearance of residual disease, tympanoplasty type and hearing outcome. A logistic regression analysis was conducted on the Potsic stage, closed or open type, TEES surgical approach and age to obtain the odds ratio for residual disease. The chance of residual disease significantly increased in the presence of an open-type congenital cholesteatoma (odds ratio: 30.82; 95 % confidence interval: 1.456–652.3; p = 0.0277), but not for any of the other factors including Potsic stage. The timing of the confirmation of residual disease after ossicular chain reconstruction was analyzed using a Kaplan-Meier analysis. The residual disease rate was significantly higher with an open-type congenital cholesteatoma (log-rank test, p < 0.05). In addition, all residual disease occurred within three years after surgery. Our results showed that an open-type congenital cholesteatoma is the strongest predictive factor for residual disease when removing a congenital cholesteatoma by TEES. [ABSTRACT FROM AUTHOR]

Background: Residual disease after neoadjuvant chemotherapy (NAC) in breast cancer patients predicts worse outcomes than pathological complete response. Differing prognostic impacts based on the anatomical site of residual tumors are not well studied. Objectives: The study aims to assess disease-free survival (DFS) in breast cancer patients with different residual tumor sites following NAC and to develop a nomogram for predicting 1- to 3-year DFS in these patients. Design: A retrospective cohort study. Methods: Retrospective analysis of 953 lymph node-positive breast cancer patients with residual disease post-NAC. Patients were categorized into three groups: residual disease in breast (RDB), residual disease in lymph nodes (RDN), and residual disease in both (RDBN). DFS compared among groups. Patients were divided into a training set and a validation set in a 7:3 ratio. Prognostic factors for DFS were analyzed to develop a nomogram prediction model. Results: RDB patients had superior 3-year DFS of 94.6% versus 85.2% for RDN and 81.8% for RDBN (p < 0.0001). Clinical T stage, N stage, molecular subtype, and postoperative pN stage were independently associated with DFS on both univariate and multivariate analyses. Nomogram integrating clinical tumor-node-metastasis (TNM) stage, molecular subtype, pathological response demonstrated good discrimination (C-index 0.748 training, 0.796 validation cohort), and calibration. Conclusion: The location of residual disease has prognostic implications, with nodal residuals predicting poorer DFS. The validated nomogram enables personalized DFS prediction to guide treatment decisions. Plain language summary: Understanding the impact of residual tumor location on prognosis after breast cancer treatment After receiving neoadjuvant chemotherapy, a treatment to shrink tumors before surgery, some breast cancer patients may still have residual tumor cells. Our study focuses on how the location of these remaining tumors – whether in the breast, lymph nodes, or both – affects the likelihood of the cancer not returning within the next 1 to 3 years. This likelihood is known as 'disease-free survival' (DFS). We analyzed data from 953 breast cancer patients who underwent neoadjuvant chemotherapy and still had residual tumors. By comparing DFS among patients with tumors remaining in different locations, we discovered that the specific location of the residual tumor significantly impacts the patient's long-term health and recovery. Additionally, we developed a predictive tool called a 'nomogram' to help doctors and patients assess the risk of cancer recurrence in the next 1 to 3 years. This tool considers various factors such as the size and type of the tumor, as well as the location and extent of the residual tumor after chemotherapy. Our research offers new insights into understanding the risk of recurrence after breast cancer treatment. This work not only enhances our comprehension of breast cancer management but also aids in devising more personalized and effective treatment strategies for patients in the future. [ABSTRACT FROM AUTHOR]

ObjectiveThe presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery.MethodsThis analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS.ResultsMenopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46-0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43-0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65-1.25, p = 0.53).ConclusionsThe association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.

Abstract Background Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated with poorer survival outcomes compared with no residual disease. We performed a meta-analysis to assess the impact of varying levels of residual disease status on survival outcomes in patients with ovarian cancer who have undergone primary cytoreductive surgery or interval cytoreductive surgery in the setting of new therapies for this disease. Methods Medline, Embase, and Cochrane databases (January 2011 – July 2020) and grey literature, bibliographic and key conference proceedings, were searched for eligible studies. Fixed and random-effects meta-analyses compared progression and survival by residual disease level across studies. Heterogeneity between comparisons was explored via type of surgery, disease stage, and type of adjuvant chemotherapy. Results Of 2832 database and 16 supplementary search articles screened, 50 studies were selected; most were observational studies. The meta-analysis showed that median progression-free survival and overall survival decreased progressively with increasing residual disease (residual disease categories of 0 cm, > 0–1 cm and > 1 cm). Compared with no residual disease, hazard ratios (HR) for disease progression increased with increasing residual disease category (1.75 [95% confidence interval: 1.42, 2.16] for residual disease > 0–1 cm and 2.14 [1.34, 3.39] for residual disease > 1 cm), and also for reduced survival (HR versus no residual disease, 1.75 [ 1.62, 1.90] for residual disease > 0–1 cm and 2.32 [1.97, 2.72] for residual disease > 1 cm). All comparisons were significant (p

Background: Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated with poorer survival outcomes compared with no residual disease. We performed a meta-analysis to assess the impact of varying levels of residual disease status on survival outcomes in patients with ovarian cancer who have undergone primary cytoreductive surgery or interval cytoreductive surgery in the setting of new therapies for this disease. Methods: Medline, Embase, and Cochrane databases (January 2011 – July 2020) and grey literature, bibliographic and key conference proceedings, were searched for eligible studies. Fixed and random-effects meta-analyses compared progression and survival by residual disease level across studies. Heterogeneity between comparisons was explored via type of surgery, disease stage, and type of adjuvant chemotherapy. Results: Of 2832 database and 16 supplementary search articles screened, 50 studies were selected; most were observational studies. The meta-analysis showed that median progression-free survival and overall survival decreased progressively with increasing residual disease (residual disease categories of 0 cm, > 0–1 cm and > 1 cm). Compared with no residual disease, hazard ratios (HR) for disease progression increased with increasing residual disease category (1.75 [95% confidence interval: 1.42, 2.16] for residual disease > 0–1 cm and 2.14 [1.34, 3.39] for residual disease > 1 cm), and also for reduced survival (HR versus no residual disease, 1.75 [ 1.62, 1.90] for residual disease > 0–1 cm and 2.32 [1.97, 2.72] for residual disease > 1 cm). All comparisons were significant (p < 0.05). Subgroup analyses showed an association between residual disease and disease progression/reduced survival irrespective of type of surgery, disease stage, or type of adjuvant chemotherapy. Conclusions: This meta-analysis provided an update on the impact of residual disease following primary or interval cytoreductive surgery, and demonstrated that residual disease was still highly predictive of progression-free survival and overall survival in adults with ovarian cancer despite changes in ovarian cancer therapy over the last decade. Higher numerical categories of residual disease were associated with reduced survival than lower categories. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that is characterized by new bone formation in the axial musculoskeletal system, with X-ray discriminating between radiographic and non-radiographic forms. Current therapeutic options include non-steroidal anti-inflammatory drugs in addition to biological disease-modifying anti-rheumatic drugs that specifically target tumor necrosis factor-alpha (TNFα) or interleukin (IL)-17. Pain is the most critical symptom for axSpA patients, significantly contributing to the burden of disease and impacting daily life. While the inflammatory process exerts a major role in determining pain in the early phases of the disease, the symptom may also result from mechanical and neuromuscular causes that require complex, multi-faceted pharmacologic and non-pharmacologic treatment, especially in the later phases. In clinical practice, pain often persists and does not respond further despite the absence of inflammatory disease activity. Cytokines involved in axSpA pathogenesis interact directly/indirectly with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling cascade, a fundamental component in the origin and development of spondyloarthropathies. The JAK/ STAT pathway also plays an important role in nociception, and new-generation JAK inhibitors have demonstrated rapid pain relief. We provide a comprehensive review of the different pain types observed in axSpA and the potential role of JAK/ STAT signaling in this context, with specific focus on data from preclinical studies and data from clinical trials with JAK inhibitors. [ABSTRACT FROM AUTHOR]

OBJECTIVE The purpose of this study was to evaluate the performance of a next-generation sequencing-based liquid biopsy test for cancer monitoring in dogs. SAMPLES Pre- and postoperative blood samples were collected from dogs with confirmed cancer diagnoses originally enrolled in the CANcer Detection in Dogs (CANDiD) study. A subset of dogs also had longitudinal blood samples collected for recurrence monitoring. METHODS All cancer-diagnosed patients had a preoperative blood sample in which a cancer signal was detected and had at least 1 postoperative sample collected. Clinical data were used to assign a clinical disease status for each follow-up visit. RESULTS Following excisional surgery, in the absence of clinical residual disease at the postoperative visit, patients with Cancer Signal Detected results at that visit were 1.94 times as likely (95% CI, 1.21 to 3.12; P = .013) to have clinical recurrence within 6 months compared to patients with Cancer Signal Not Detected results. In the subset of patients with longitudinal liquid biopsy samples that had clinical recurrence documented during the study period, 82% (9/11; 95% CI, 48% to 97%) had Cancer Signal Detected in blood prior to or concomitant with clinical recurrence; in the 6 patients where molecular recurrence was detected prior to clinical recurrence, the median lead time was 168 days (range, 47 to 238). CLINICAL RELEVANCE Next-generation sequencing-based liquid biopsy is a noninvasive tool that may offer utility as an adjunct to current standard-of-care clinical assessment for cancer monitoring; further studies are needed to confirm diagnostic accuracy in a larger population. [ABSTRACT FROM AUTHOR]

Background: Prognosis of perihilar cholangiocarcinoma (PHCC) is poor, and curative-intent resection is the most effective treatment associated with long-term survival. Surgery is technically demanding since it involves a major hepatectomy with en bloc resection of the caudate lobe and extrahepatic bile duct. Furthermore, to achieve negative margins, it may be necessary to perform concomitant vascular resection or pancreatoduodenectomy. Despite this aggressive approach, recurrence is often observed, considering 5-year recurrence-free survival below 15% and 5-year overall survival that barely exceeds 40%. Summary: The literature reports that survival rates are better in patients with negative margins, and surprisingly, R0 resections range between 19% and 95%. This variability is probably due to different surgical strategies and the pathologist's expertise with specimens. In fact, a proper pathological examination of residual disease should take into consideration both the ductal and the radial margin (RM) status. Currently, detailed pathological reports are lacking, and there is a likelihood of misinterpreting residual disease status due to the missing of RM description and the utilization of various definitions for surgical margins. Key Messages: The aim of PHCC surgery is to achieve negative margins including RM. More clarity in reporting on RM is needed to define true radical resection and consistent design of oncological studies for adjuvant treatments. [ABSTRACT FROM AUTHOR]

Background: Breast cancer patients with residual disease after neoadjuvant systemic treatment (NAST) have a worse prognosis compared with those achieving a pathologic complete response (pCR). Earlier identification of these patients might allow timely, extended neoadjuvant treatment strategies. We explored the feasibility of a vacuum-assisted biopsy (VAB) after NAST to identify patients with residual disease (ypT+ or ypN+) prior to surgery. Methods: We used data from a multicenter trial, collected at 21 study sites (NCT02948764). The trial included women with cT1-3, cN0/+ breast cancer undergoing routine post-neoadjuvant imaging (ultrasound, MRI, mammography) and VAB prior to surgery. We compared the findings of VAB and routine imaging with the histopathologic evaluation of the surgical specimen. Results: Of 398 patients, 34 patients with missing ypN status and 127 patients with luminal tumors were excluded. Among the remaining 237 patients, tumor cells in the VAB indicated a surgical non-pCR in all patients (73/73, positive predictive value [PPV] 100%), whereas PPV of routine imaging after NAST was 56.0% (75/134). Sensitivity of the VAB was 72.3% (73/101), and 74.3% for sensitivity of imaging (75/101). Conclusion: Residual cancer found in a VAB specimen after NAST always corresponds to non-pCR. Residual cancer assumed on routine imaging after NAST corresponds to actual residual cancer in about half of patients. Response assessment by VAB is not safe for the exclusion of residual cancer. Response assessment by biopsies after NAST may allow studying the new concept of extended neoadjuvant treatment for patients with residual disease in future trials. [ABSTRACT FROM AUTHOR]

Purpose: Achieving no residual disease is essential for increasing overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients. However, the survival benefit of achieving no residual disease during both intrathoracic and abdominopelvic cytoreductive surgery is still unclear. This meta-analysis aimed to assess the survival benefit and safety of intrathoracic and abdominopelvic cytoreductive surgery in advanced ovarian cancer patients. Methods: We systematically searched for studies in online databases, including PubMed, Embase, and Web of Science. We used Q statistics and I-squared statistics to evaluate heterogeneity, sensitivity analysis to test the origin of heterogeneity, and Egger's and Begg's tests to evaluate publication bias. Results: We included 4 retrospective cohort studies, including 490 patients, for analysis; these studies were assessed as high-quality studies. The combined hazard ratio (HR) with 95% confidence interval (CI) for OS was 1.92 (95% CI 1.38-2.68), while the combined HR for PFS was 1.91 (95% CI 1.47-2.49). Only 19 patients in the four studies reported major complications, and 4 of these complications were surgery related. Conclusion: The maximal extent of cytoreduction in the intrathoracic and abdominopelvic tract improves survival outcomes, including OS and PFS, in advanced ovarian cancer patients with acceptable complications. [ABSTRACT FROM AUTHOR]

Background: The persistence of residual tumour after neoadjuvant chemotherapy (NAC) in localised triple-negative breast cancer (TNBC) is known to have a negative prognostic value. However, different degrees of expression of some immunohistochemical markers may correlate with different prognoses. Methods: The expression of biomarkers with a known prognostic value, i.e., cytokeratin 5/6 (CK5/6), androgen receptor (AR), epidermal growth factor receptor (EGFR) proliferation-related nuclear antigen Ki-67, human epidermal growth factor receptor 2 (HER2), protein 53 (p53), forkhead box protein 3 (FOXP3), and cluster differentiation 8 (CD8), was analysed by immunohistochemistry in 111 samples after NAC in non-metastatic TNBC patients addressed to Georges-Francois Leclerc Cancer Centre Dijon, France. Clinical and pathological variables were retrospectively collected. Cox regression was used to identify immunohistochemical (IHC) and clinicopathological predictors of event-free survival (EFS) (relapse or death). Results: Median age was 50.4 years (range 25.6-88.3), 55.9% (n = 62) were non-menopausal, 70 (63.1%) had stage IIA-IIB disease. NAC was mostly sequential anthracycline-taxanes (72.1%), and surgical intervention was principally conservative (51.3%). We found 65.7% ypT1, 47.2% lymph node involvement (ypN+), and 29.4% lymphovascular invasion (LVI). Most residual tumours were EGFR >110 (H-score) (60.5%, n = 66), AR ≤4% (53.2%, n = 58), p53-positive mutated (52.7%, n = 58), CD8 ≤26 (58.1%, n = 61), FOXP3 =7 (51.4%, n = 54), more than half in the stroma, and 52.3% (n = 58) HER2 score 0. After a median follow-up of 80.8 months, 48.6% had relapsed. Median EFS was 62.3 months (95% CI, 37.2-not reached (NR)). Factors independently associated with poor EFS were AR-low (p = 0.002), ypN+ (p < 0.001), and LVI (p = 0.001). Factors associated with lower overall survival (OS) were EGFRlow (p = 0.041), Ki-67 high (p = 0.024), and ypN+ (p < 0.001). Conclusion: Post-NAC residual disease in TNBC showed biomarkers specific to a basal-like subtype and markers of lymphocyte infiltration mostly present in the stroma. Prognostic markers for EFS were AR, LVI, and ypN and warrant further validation in a prognostic model. [ABSTRACT FROM AUTHOR]

Simple Summary: Unplanned excision (UE) of soft tissue sarcomas represents an important issue when treating this group of rare malignancies. It has been reported that UE may result in a poorer prognosis in terms of recurrence, survival, and other factors such as the need for amputation and plastic reconstruction procedures. Through a systematic review and meta-analysis of the available evidence, we aimed to answer some of the more relevant questions regarding oncological outcomes in these patients. Our study is the largest of its kind, and includes several important studies published over the last 5 years. We identified an association between unplanned excision and local recurrence, with special consideration to the impact of residual disease after an unplanned excision on local recurrence, and an association of local recurrence and worse overall survival in soft tissue sarcoma patients. Orthopaedic surgeons should consider re-excision as the standard approach when dealing with unplanned excision. Background: Soft tissue sarcomas are a group of rare neoplasms which can be mistaken for benign masses and be excised in a non-oncologic fashion (unplanned excision). Whether unplanned excision (UE) is associated with worse outcomes is highly debated due to conflicting evidence. Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. Main outcomes analyzed were five-year overall survival (OS), five-year local recurrence-free survival (LRFS), amputation rate and plastic reconstruction surgery rate. Risk ratios were used to compare outcomes between patients treated with planned and unplanned excision. Results: We included 16,946 patients with STS, 6017 (35.5%) with UE. UE was associated with worse five-year LRFS (RR 1.35, p = 0.019). Residual tumor on the tumor bed was associated with lower five-year LRFS (RR = 2.59, p < 0.001). Local recurrence was associated with worse five-year OS (RR = 1.82, p < 0.001). UE was not associated with a worse five-year OS (RR = 0.90, p = 0.16), higher amputation rate (RR = 0.77, p = 0.134), or a worse plastic reconstruction surgery rate (RR = 1.25, p = 0.244). Conclusions: Unplanned excision of Soft Tissue Sarcomas and the presence of disease in tumor bed after one were associated with worse five-year LRFS. Tumor bed excision should remain the standard approach, with special consideration to the presence of residual disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Romania ranks second in Europe in both mortality and incidence rates for cervical cancer, and the majority of cases are diagnosed in locally advanced stages. Therapeutic guidelines indicate concomitant chemoradiotherapy as the proper treatment (total dose 85–90 Gy at point A). Yet, in Romania, as a result of poor radiotherapy infrastructure, deficient patient access to radiotherapy, and specific socio-psychologic factors, concurrent chemoradiotherapy is usually suboptimal (total dose 60–65 Gy at point A) and often followed by radical surgery aimed at better local control. Our retrospective cohort study of 351 patients with histopathological confirmed locally advanced cervical cancer proved that complete pathologic response is present in less than half of patients previously treated by concurrent chemoradiotherapy, thus demonstrating the rationale behind radical surgery—better local control, especially in unfavorable aggressive histological types like adenocarcinoma and adenosquamous carcinoma or tumors that have progressed under concurrent chemoradiotherapy. We discuss several possible causes for the over-usage of surgery in Romania for treating locally advanced cervical cancer. The incidence and mortality of cervical cancer are high in Romania compared to other European countries, particularly for locally advanced cervical cancer cases, which are predominant at the time of diagnosis. Widely accepted therapeutic guidelines indicate that the treatment for locally advanced cervical cancer consists of concurrent chemoradiotherapy (total dose 85–90 Gy at point A), with surgery not being necessary as it does not lead to improved survival and results in significant additional morbidity. In Romania, the treatment for locally advanced cervical cancer differs, involving lower-dose chemoradiotherapy (total dose 60–65 Gy at point A), followed by surgery, which, under these circumstances, ensures better local control. In this regard, we attempted to evaluate the role and necessity of surgery in Romania, considering that in our study, residual lesions were found in 55.84% of cases on resected specimens, especially in cases with unfavorable histology (adenocarcinoma and adenosquamous carcinoma). This type of surgery was associated with significant morbidity (28.22%) in our study. The recurrence rate was 24.21% for operated-on patients compared to 62% for non-operated-on patients receiving suboptimal concurrent chemotherapy alone. In conclusion, in Romania, surgery will continue to play a predominant role until radiotherapy achieves the desired effectiveness for local control. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with locally advanced cervical cancer, there is still a high reported locoregional recurrence rate after chemoradiation therapy. Therefore, timely detection of locoregional residual disease is important for patients to be treated with salvage surgery. Furthermore, it is important to select only the patients who would benefit from salvage surgery and not to expose patients unnecessarily to the risks of surgery. Therefore, the aim of this study is to assess two different imaging techniques, MRI and 18F[FDG]-PET/CT, for their ability to determine the presence of locoregional residual disease after chemoradiotherapy in patients with locally advanced cervical cancer. MRI and 18F[FDG]-PET/CT were compared with pathology-proven locoregional residual disease or locoregional recurrence identified from biopsy and/or salvage surgery. The findings from this research provide insights into the ability of MRI and 18F[FDG]-PET/CT to detect locoregional residual disease. Objectives: There is no consensus on the most reliable procedure to determine remission of cervical cancer after chemoradiotherapy (CRT). Therefore, this study aims to assess the diagnostic performance of two different imaging techniques, MRI and 18F[FDG]-PET/CT, in determining the presence of locoregional residual disease after CRT in patients with locally advanced cervical cancer. Methods: Patients diagnosed with locally advanced cervical cancer (FIGO 2009) treated with CRT were retrospectively identified from a regional cohort. The accuracy of MRI and 18F[FDG]-PET/CT in detecting locoregional residual disease was assessed with histology as the reference standard. Results: The negative predictive value (NPV) and positive predictive value (PPV) for locoregional residual disease detection of MRI and 18F[FDG]-PET/CT combined were 84.2% (95% CI 73.2–92.1), and 70.4% (95% CI 51.8–85.2), respectively. The NPV and PPV of MRI alone were 80.2% (95% CI 71.2–87.5) and 47.7% (95% CI 35.8–59.7), respectively, and values of 81.1% (95% CI 72.2–88.3) and 55.8 (95% CI 42.2–68.7), respectively, were obtained for 18F[FDG]-PET/CT alone. Conclusion: In this study, the reliability of MRI and 18F[FDG]-PET/CT in detecting locoregional residual disease was limited. Combining MRI and 18F[FDG]-PET/CT did not improve predictive values. Routine use of both MRI and 18F[FDG]-PET/CT in the follow-up after CRT should be avoided. MRI during follow-up is the advised imaging technique. Pathology confirmation of the presence of locoregional residual disease before performing salvage surgery is warranted. [ABSTRACT FROM AUTHOR]

Abstract Background No residual disease (R0 resection) after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models. Methods RNA sequencing of circulating small extracellular vesicles (sEVs) was used to discover the differential expression microRNAs (DEMs) profile between any residual disease (R0, n = 17) and no residual disease (non-R0, n = 20) in AOC patients. We further analyzed plasma samples of AOC patients collected before surgery or neoadjuvant chemotherapy via TaqMan qRT-PCR. The combined risk model of residual disease was developed by logistic regression analysis based on the discovery-validation sets. Results Using a comprehensive plasma small extracellular vesicles (sEVs) microRNAs (miRNAs) profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA and CA-125 with better performance in predicting R0 resection. Based on 360 clinical human samples, this model was constructed using least absolute shrinkage and selection operator (LASSO) and logistic regression analysis, and it has favorable calibration and discrimination ability (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (NRI = 0.471, IDI = 0.538, p

Background: No residual disease (R0 resection) after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models. Methods: RNA sequencing of circulating small extracellular vesicles (sEVs) was used to discover the differential expression microRNAs (DEMs) profile between any residual disease (R0, n = 17) and no residual disease (non-R0, n = 20) in AOC patients. We further analyzed plasma samples of AOC patients collected before surgery or neoadjuvant chemotherapy via TaqMan qRT-PCR. The combined risk model of residual disease was developed by logistic regression analysis based on the discovery-validation sets. Results: Using a comprehensive plasma small extracellular vesicles (sEVs) microRNAs (miRNAs) profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA and CA-125 with better performance in predicting R0 resection. Based on 360 clinical human samples, this model was constructed using least absolute shrinkage and selection operator (LASSO) and logistic regression analysis, and it has favorable calibration and discrimination ability (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (NRI = 0.471, IDI = 0.538, p < 0.001; NRI = 0.122, IDI = 0.185, p < 0.01). Conclusion: Overall, we established a reliable, non-invasive, and objective detection method composed of circulating tumor-derived sEVs 4-miRNA plus CA-125 to preoperatively anticipate the high-risk AOC patients of residual disease to optimize clinical therapy. [ABSTRACT FROM AUTHOR]

Current treatment strategies for primary epithelial ovarian cancer (EOC) have significantly evolved, and the value of complete cytoreduction has not yet been reassessed. The study aimed to investigate the impact of residual disease after cytoreductive surgery for EOC on survival outcomes within the recent paradigm of frontline ovarian cancer treatment. We searched relevant literature from the MEDLINE, Embase, and Cochrane Library databases to identify randomized controlled trials and prospective clinical trials of primary EOC published between 1 January 2000 and 22 September 2022. To evaluate the impact of postoperative residual tumors on progression-free survival (PFS) and OS, we constructed a linear regression model for log-transformed median PFS and OS. Patients who did or did not receive first-line maintenance therapy were examined. A total of 97 trials with 43,260 patients were included:2476 received poly(ADP-ribose) polymerase (PARP) inhibitors and 6587 received bevacizumab. Multivariable analysis of the linear regression model of all studies revealed that the median OS increased by 12.97% for every 10% increase in complete cytoreduction rates, independent of the use of systemic maintenance. In the subgroup analysis of patients receiving maintenance therapies, the effect of complete tumor clearance was potentiated, with a median OS increase of 19.13% for every 10% increase in complete cytoreduction rates. Total macroscopic tumor clearance at the initial presentation of EOC significantly prolongs OS. Our results establish the importance of complete surgical cytoreduction, even after the introduction of recent advances in frontline treatment for EOC. • Treatment strategies for primary EOC have evolved, but complete cytoreduction's value remains unassessed. • 97 trials, 43,260 patients, studied residual disease impact on EOC survival after surgery in this meta-analysis. • 10% rise in complete cytoreduction rate linked to a 12.97% increase in median log overall survival. [ABSTRACT FROM AUTHOR]

Purpose: Risk assessment of disease recurrence in pT1 colorectal cancer is crucial in order to select the appropriate treatment strategy. The study aimed to develop a prediction model, based on histopathological data, for the probability of disease recurrence and residual disease in patients with pT1 colorectal cancer. Methods: The model dataset consisted of 558 patients with pT1 CRC who had undergone endoscopic resection only (n = 339) or endoscopic resection followed by subsequent bowel resection (n = 219). Tissue blocks and slides were retrieved from Pathology Departments from all regions in Denmark. All original slides were evaluated by one experienced gastrointestinal pathologist (TPK). New sections were cut and stained for haematoxylin and eosin (HE) and immunohistochemical markers. Missing values were multiple imputed. A logistic regression model with backward elimination was used to construct the prediction model. Results: The final prediction model for disease recurrence demonstrated good performance with AUC of 0.75 [95% CI 0.72–0.78], HL chi-squared test of 0.59 and scaled Brier score of 10%. The final prediction model for residual disease demonstrated medium performance with an AUC of 0.68 [0.63–0.72]. Conclusion: We developed a prediction model for the probability of disease recurrence in pT1 CRC with good performance and calibration based on histopathological data. Together with lymphatic and venous invasion, an involved resection margin (0 mm) as opposed to a margin of ≤ 1 mm was an independent risk factor for both disease recurrence and residual disease. [ABSTRACT FROM AUTHOR]

Objective. To explore residual disease, defined as substantial symptoms and disease burden despite a remission or low disease activity (LDA) state, in patients with axial spondyloarthritis (axSpA), and to determine which factors are associated with residual disease. Methods. For this cross-sectional observational study, 1 timepoint per patient was used from SpA-Net, a web-based monitoring registry for SpA. Patients with an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 (LDA) were included. Indicators of residual disease (outcomes) included fatigue (primary outcome), pain, physical functioning, health-related quality of life (HRQOL), and peripheral symptoms. Sex was the primary explanatory factor for residual disease. Other explanatory factors included demographics and disease-related factors. Associations between these factors and presence and extent of residual disease were explored using logistic and linear regression. Results. In total, 267 patients in an LDA state were included. Mean age was 50.6 (SD 14.3) years and 100 (37.5%) were female. Residual disease occurred frequently (n = 114 [42.7%] had fatigue scores > 4/10; n = 34 [17.8%] had pain scores > 4/10), including in those in remission (ASDAS < 1.3). Physical HRQOL was reduced in 27% and moderate/poor in 33%. Multivariable regression analyses showed that reported fatigue was more severe and prevalent in female patients (fatigue severity [0-10]: Bfemale = 0.78, 95% CI 0.18-1.38; fatigue > 4/10: ORfemale = 3.29, 95% CI 1.74-6.20). Other indicators of residual disease (ie, pain, peripheral symptoms, physical HRQOL) were also more severe and/or more prevalent in females. Conclusion. Residual disease is frequent in patients with axSpA who are in an LDA state, including remission, and it is particularly prevalent in female patients. Future studies should address how to manage or prevent residual disease in axSpA. [ABSTRACT FROM AUTHOR]

The therapeutic armamentarium for the neoadjuvant treatment of triple-negative breast cancer (TNBC) has significantly expanded with the hopes of improving pathological complete response (pCR) rates and the possibility of a cure. However, the data on optimal adjuvant treatment strategies for patients with residual disease after neoadjuvant treatment is limited. We discuss the available data on adjuvant treatment for residual TNBC after neoadjuvant treatment considering clinical trials. Additionally, we discuss ongoing trials to give perspectives on how the field may evolve in the next decade. The available data support the use of adjuvant capecitabine for all patients and either adjuvant capecitabine or olaparib for patients with germline BRCA1 and BRCA2 mutations, according to availability. The CREATE-X study of capecitabine and OlympiA study of olaparib demonstrated disease-free and overall survival benefits. There is an unmet need for studies comparing these two options for patients with germline BRCA mutations. Further research is needed to delineate the use of immunotherapy in the adjuvant setting, molecular targeted therapy for patients with molecular alterations other than germline BRCA mutation, combinations, and antibody-drug conjugates to further improve outcomes. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that is characterized by new bone formation in the axial musculoskeletal system, with X-ray discriminating between radiographic and non-radiographic forms. Current therapeutic options include non-steroidal anti-inflammatory drugs in addition to biological disease-modifying anti-rheumatic drugs that specifically target tumor necrosis factor-alpha (TNFα) or interleukin (IL)-17. Pain is the most critical symptom for axSpA patients, significantly contributing to the burden of disease and impacting daily life. While the inflammatory process exerts a major role in determining pain in the early phases of the disease, the symptom may also result from mechanical and neuromuscular causes that require complex, multi-faceted pharmacologic and non-pharmacologic treatment, especially in the later phases. In clinical practice, pain often persists and does not respond further despite the absence of inflammatory disease activity. Cytokines involved in axSpA pathogenesis interact directly/indirectly with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling cascade, a fundamental component in the origin and development of spondyloarthropathies. The JAK/STAT pathway also plays an important role in nociception, and new-generation JAK inhibitors have demonstrated rapid pain relief. We provide a comprehensive review of the different pain types observed in axSpA and the potential role of JAK/STAT signaling in this context, with specific focus on data from preclinical studies and data from clinical trials with JAK inhibitors.

BackgroundThe persistence of residual tumour after neoadjuvant chemotherapy (NAC) in localised triple-negative breast cancer (TNBC) is known to have a negative prognostic value. However, different degrees of expression of some immunohistochemical markers may correlate with different prognoses.MethodsThe expression of biomarkers with a known prognostic value, i.e., cytokeratin 5/6 (CK5/6), androgen receptor (AR), epidermal growth factor receptor (EGFR) proliferation-related nuclear antigen Ki-67, human epidermal growth factor receptor 2 (HER2), protein 53 (p53), forkhead box protein 3 (FOXP3), and cluster differentiation 8 (CD8), was analysed by immunohistochemistry in 111 samples after NAC in non-metastatic TNBC patients addressed to Georges-François Leclerc Cancer Centre Dijon, France. Clinical and pathological variables were retrospectively collected. Cox regression was used to identify immunohistochemical (IHC) and clinicopathological predictors of event-free survival (EFS) (relapse or death).ResultsMedian age was 50.4 years (range 25.6–88.3), 55.9% (n = 62) were non-menopausal, 70 (63.1%) had stage IIA–IIB disease. NAC was mostly sequential anthracycline-taxanes (72.1%), and surgical intervention was principally conservative (51.3%). We found 65.7% ypT1, 47.2% lymph node involvement (ypN+), and 29.4% lymphovascular invasion (LVI). Most residual tumours were EGFR >110 (H-score) (60.5%, n = 66), AR ≥4% (53.2%, n = 58), p53-positive mutated (52.7%, n = 58), CD8 ≥26 (58.1%, n = 61), FOXP3 ≥7 (51.4%, n = 54), more than half in the stroma, and 52.3% (n = 58) HER2 score 0. After a median follow-up of 80.8 months, 48.6% had relapsed. Median EFS was 62.3 months (95% CI, 37.2–not reached (NR)). Factors independently associated with poor EFS were AR-low (p = 0.002), ypN+ (p < 0.001), and LVI (p = 0.001). Factors associated with lower overall survival (OS) were EGFR-low (p = 0.041), Ki-67 high (p = 0.024), and ypN+ (p < 0.001).ConclusionPost-NAC residual disease in TNBC showed biomarkers specific to a basal-like subtype and markers of lymphocyte infiltration mostly present in the stroma. Prognostic markers for EFS were AR, LVI, and ypN and warrant further validation in a prognostic model.

Abstract Background Sensitive and reproducible detection of residual disease after treatment is a major challenge for patients with locally advanced head and neck cancer. Indeed, the current imaging techniques are not always reliable enough to determine the presence of residual disease. The aim of the NeckTAR trial is to assess the ability of circulating DNA (cDNA), both tumoral and viral, at three months post-treatment, to predict residual disease, at the time of the neck dissection, among patients with partial cervical lymph node response on PET-CT, after potentiated radiotherapy. Methods This will be an interventional, multicentre, single-arm, open-label, prospective study. A blood sample will be screened for cDNA before potentiated radiotherapy and after 3 months if adenomegaly persists on the CT scan 3 months after the end of treatment. Patients will be enrolled in 4 sites in France. Evaluable patients, i.e. those with presence of cDNA at inclusion, an indication for neck dissection, and a blood sample at M3, will be followed for 30 months. Thirty-two evaluable patients are expected to be recruited in the study. Discussion The decision to perform neck dissection in case of persistent cervical adenopathy after radio-chemotherapy for locally advanced head and neck cancer is not always straightforward. Although studies have shown that circulating tumour DNA is detectable in a large proportion of patients with head and neck cancer, enabling the monitoring of response, the current data is insufficient to allow routine use of this marker. Our study could lead to better identification of patients who do not have residual lymph node disease in order to avoid neck dissection and preserve their quality-of-life while maintaining their prospects of survival. Trial registration Clinicaltrials.gov: NCT05710679, registered on 02/02/2023, https://clinicaltrials.gov/ct2/show/ . Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID RCB 2022-A01668-35, registered on July 15th, 2022.

Quality of life evaluation is a cornerstone of randomized controlled trials in hematology but is now rarely considered as such, and is a often only a secondary endpoint in most studies. For CLL patients, how can we abandon PFS to move to OS in good QOL? [ABSTRACT FROM AUTHOR]

Abstract Background The changes in prognostic factors and clinicopathological characteristics of residual disease following neoadjuvant therapy (NAT) for breast cancer are important references for postoperative adjuvant therapy. The analyses of the relationship between the clinicopathological characteristics of residual diseases and the prognosis were not comprehensive in most previous studies. This study aimed to determine how prognostic factors changed following NAT and the impact of clinicopathological characteristics of residual disease on the prognosis of human epidermal growth factor receptor 2 (HER2)‐positive breast cancer. Methods The study comprised 350 consecutive patients with HER2‐positive breast cancer who had residual disease after surgery following NAT. The independent risk factors affecting the prognosis of HER2‐positive breast cancer were analyzed using univariate and multivariate Cox regression analyses. Chi‐square test and binary logistic regression were used to analyze the influencing factors of HER2 loss following NAT. Results The expression of prognostic factors changed significantly following NAT. A total of 44 patients (12.6%) had HER2 loss. HER2 status (immunohistochemistry (IHC) 3+ vs. IHC 2+/FISH+, p

Introduction: Primary debulking surgery (PDS), interval debulking surgery (IDS), and platinum-based chemotherapy are the current standard treatments for advanced ovarian cancer (OC). The time to initiation of adjuvant chemotherapy (TTC) could influence patient outcomes. Methods: We conducted a multicenter retrospective cohort study of advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) OC treated between 2014 and 2018 to assess progression-free survival (PFS) and overall survival (OS) in relation to TTC. All patients underwent a germline multigene panel for BRCA1/2 evaluation. Results: Among the 83 patients who underwent PDS, a TTC ≥ 60 days was associated with a shorter PFS (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.04--3.93, p = 0.038), although this association lost statistical significance when adjusting for residual disease (HR 1.52, 95% CI 0.75-3.06, p = 0.244, for TTC and HR 2.73, 95% CI 1.50-4.96, p = 0.001, for residual disease). Among 52 IDS patients, we found no evidence of an association between TTC and clinical outcomes. Ascites, type of chemotherapy, or germline BRCA1/2 mutational status did not influence TTC and were not associated with clinical outcomes in PDS or IDS patients. Discussion: In conclusion, longer TTC seems to negatively affect prognosis in patients undergoing PDS, especially those with residual disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Long-term population-based studies have demonstrated that the risk of cervical cancer after conization for CIN3 treatment persists for at least 25 years, underscoring the need for careful follow ups and the importance of detecting residual disease after LEEP. Data from the literature show that positive-margin and post-treatment HPV persistence are predictors of residual disease. The management of these cases determines the use of a second LEEP or an accurate follow up, but the risk of overtreatment or of not treating an occult carcinoma exists. Our goal was to discover an efficient method to select patients requiring a second LEEP from those requiring a follow up (FU) only through the use of E6/E7 HPV mRNA search. This prognostic marker allowed us to identify women with residual disease (CIN2+) and treat them with a second LEEP. At the same time, it helped us identify E6/E7-mRNA-negative women as patients at low risk of progression, potentially avoiding further treatment and subjecting them to a follow up only. The risk of overtreatment or not treating an occult carcinoma exists in women at risk of residual disease after a LEEP excision for CIN3. Our goal was to discover an efficient method to select patients requiring a second LEEP from those requiring a FU only through an mRNA-detection test. In a population of 686 women undergoing a LEEP excision for CIN 3, we selected 285 women at risk of residual disease and subjected them to a search for E6/E7 mRNA HPV. The women with negative mRNA were subjected to a follow up, while the women with positive mRNA were subjected to a second LEEP. The histological examination of the second cone revealed 120 (85.7%) cases of residual disease in the mRNA-positive women: 40 cases of CIN2, 51 cases of CIN3, 11 cases of squamous microinvasive carcinoma, 7 cases of squamous carcinoma, 9 cases of AIS (adenocarcinoma in situ) and 2 cases of adenocarcinoma. Among the mRNA-negative women undergoing a follow up, there were only five cases of residual disease. During the follow-up period of about 6 years, we witnessed the regression of the residual disease and the elimination of the virus, just as predicted by the negative result of the mRNA test. Testing patients for E6/E7 mRNA allowed us to identify women with residual disease (CIN2+) and treat them appropriately. [ABSTRACT FROM AUTHOR]

Well-differentiated gastric, duodenal, and rectal neuroendocrine neoplasms (NETs) are rare diseases usually managed by endoscopic treatment. Although several endoscopic techniques are available, the number of patients with incomplete (R1) resection is significant. This review focuses on the meaning of incomplete R1 findings after endoscopic resection in type I gastric NETs; nonfunctioning, non-ampullary duodenal NETs; and small rectal NETs. Data were identified by MEDLINE database search without publication date limitation. An incomplete R1 finding may have no significant impact on a patient's clinical outcome, particularly in small G1 type I gastric NETs, which have an indolent course. A 'stepwise approach,' which uses more advanced endoscopic techniques, or minimally invasive surgery may be justified to achieve complete margin-free resection. This approach must balance the tumor features and the procedure-related risk of complications, particularly in the duodenum, where the role of deep endoscopic resections is limited due to the thin duodenal wall. Gastric and rectal NETs that are incompletely removed after initial resection are more easily amenable to deep endoscopic techniques. However, this might not be necessary for patients with comorbidities, elderly, or both due to the uncertainty of how R1 finding impacts a patient's clinical outcome. [ABSTRACT FROM AUTHOR]

Background: Sensitive and reproducible detection of residual disease after treatment is a major challenge for patients with locally advanced head and neck cancer. Indeed, the current imaging techniques are not always reliable enough to determine the presence of residual disease. The aim of the NeckTAR trial is to assess the ability of circulating DNA (cDNA), both tumoral and viral, at three months post-treatment, to predict residual disease, at the time of the neck dissection, among patients with partial cervical lymph node response on PET-CT, after potentiated radiotherapy. Methods: This will be an interventional, multicentre, single-arm, open-label, prospective study. A blood sample will be screened for cDNA before potentiated radiotherapy and after 3 months if adenomegaly persists on the CT scan 3 months after the end of treatment. Patients will be enrolled in 4 sites in France. Evaluable patients, i.e. those with presence of cDNA at inclusion, an indication for neck dissection, and a blood sample at M3, will be followed for 30 months. Thirty-two evaluable patients are expected to be recruited in the study. Discussion: The decision to perform neck dissection in case of persistent cervical adenopathy after radio-chemotherapy for locally advanced head and neck cancer is not always straightforward. Although studies have shown that circulating tumour DNA is detectable in a large proportion of patients with head and neck cancer, enabling the monitoring of response, the current data is insufficient to allow routine use of this marker. Our study could lead to better identification of patients who do not have residual lymph node disease in order to avoid neck dissection and preserve their quality-of-life while maintaining their prospects of survival. Trial registration: Clinicaltrials.gov: NCT05710679, registered on 02/02/2023, https://clinicaltrials.gov/ct2/show/. Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID RCB 2022-A01668-35, registered on July 15th, 2022. [ABSTRACT FROM AUTHOR]

Background: Patients with a biopsy-confirmed cervical intraepithelial neoplasia 2 and 3 have an increased risk of disease progression to invasive cancer and should be treated with an excisional method. However, after treatment with an excisional method, a high-grade residual lesion may remain in patients with positive surgical margins. We aimed to investigate the risk factors for a residual lesion in patients with a positive surgical margin after cervical cold knife conization. Methods: Records of 1008 patients who underwent conization at a tertiary gynecological cancer center were retrospectively reviewed. One hundred and thirteen patients with a positive surgical margin after cold knife conization were included in the study. We have retrospectively analyzed the characteristics of the patients treated with re-conization or hysterectomy. Results: Residual disease was identified in 57 (50.4%) patients. The mean age of the patients with residual disease was 42.47 ± 8.75 years. Age greater than 35 years (P = 0.002; OR, 4.926; 95%CI [Confidence Interval] - 1.681-14.441), more than one involved quadrant (P = 0.003; OR, 3.200; 95% CI - 1.466-6.987), and glandular involvement (P = 0.002; OR, 3.348; 95% CI - 1.544-7.263) were risk factors for residual disease. The rate of high-grade lesion positivity in post-conization endocervical biopsy at initial conization was similar between patients with and without residual disease (P = 0.16). The final pathology of the residual disease was microinvasive cancer in four patients (3.5%) and invasive cancer in one patient (0.9%). Conclusion: In conclusion, residual disease is found in about half of the patients with a positive surgical margin. In particular, we found that age greater than 35 years, glandular involvement, and more than 1 involved quadrant were associated with the residual disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of stereotactic body radiation therapy (SBRT) delivered after external-beam fractionated irradiation in non-small-cell lung cancer (NSCLC) patients with clinical stage III A, B. Materials and methods: All patients received three-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiation therapy (IMRT) (60–66 Gy/30–33 fractions of 2 Gy/5 days a week) with or without concomitant chemotherapy. Within 60 days from the end of irradiation, a SBRT boost (12–22 Gy in 1–3 fractions) was delivered on the residual disease. Results: Here we report the mature results of 23 patients homogeneously treated and followed up for a median time of 5.35 years (range 4.16–10.16). The rate of overall clinical response after external beam and stereotactic boost was 100%. No treatment-related mortality was recorded. Radiation-related acute toxicities with a grade ≥ 2 were observed in 6/23 patients (26.1%): 4/23 (17.4%) had esophagitis with mild esophageal pain (G2); in 2/23 (8.7%) clinical radiation pneumonitis G2 was observed. Lung fibrosis (20/23 patients, 86.95%) represented a typical late tissue damage, which was symptomatic in one patient. Median disease-free survival (DFS) and overall survival (OS) were 27.8 (95% CI, 4.2–51.3) and 56.7 months (95% CI, 34.9–78.5), respectively. Median local progression-free survival (PFS) was 17 months (range 11.6–22.4), with a median distant PFS of 18 months (range 9.6–26.4). The 5-year actuarial DFS and OS rates were 28.7% and 35.2%, respectively. Conclusions: We confirm that a stereotactic boost after radical irradiation is feasible in stage III NSCLC patients. All fit patients who have no indication to adjuvant immunotherapy and presenting residual disease after curative irradiation could benefit from stereotactic boost because outcomes seem to be better than might be historically assumed. [ABSTRACT FROM AUTHOR]

The incidence and mortality of cervical cancer are high in Romania compared to other European countries, particularly for locally advanced cervical cancer cases, which are predominant at the time of diagnosis. Widely accepted therapeutic guidelines indicate that the treatment for locally advanced cervical cancer consists of concurrent chemoradiotherapy (total dose 85–90 Gy at point A), with surgery not being necessary as it does not lead to improved survival and results in significant additional morbidity. In Romania, the treatment for locally advanced cervical cancer differs, involving lower-dose chemoradiotherapy (total dose 60–65 Gy at point A), followed by surgery, which, under these circumstances, ensures better local control. In this regard, we attempted to evaluate the role and necessity of surgery in Romania, considering that in our study, residual lesions were found in 55.84% of cases on resected specimens, especially in cases with unfavorable histology (adenocarcinoma and adenosquamous carcinoma). This type of surgery was associated with significant morbidity (28.22%) in our study. The recurrence rate was 24.21% for operated-on patients compared to 62% for non-operated-on patients receiving suboptimal concurrent chemotherapy alone. In conclusion, in Romania, surgery will continue to play a predominant role until radiotherapy achieves the desired effectiveness for local control.

Background: Soft tissue sarcomas are a group of rare neoplasms which can be mistaken for benign masses and be excised in a non-oncologic fashion (unplanned excision). Whether unplanned excision (UE) is associated with worse outcomes is highly debated due to conflicting evidence. Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. Main outcomes analyzed were five-year overall survival (OS), five-year local recurrence-free survival (LRFS), amputation rate and plastic reconstruction surgery rate. Risk ratios were used to compare outcomes between patients treated with planned and unplanned excision. Results: We included 16,946 patients with STS, 6017 (35.5%) with UE. UE was associated with worse five-year LRFS (RR 1.35, p = 0.019). Residual tumor on the tumor bed was associated with lower five-year LRFS (RR = 2.59, p < 0.001). Local recurrence was associated with worse five-year OS (RR = 1.82, p < 0.001). UE was not associated with a worse five-year OS (RR = 0.90, p = 0.16), higher amputation rate (RR = 0.77, p = 0.134), or a worse plastic reconstruction surgery rate (RR = 1.25, p = 0.244). Conclusions: Unplanned excision of Soft Tissue Sarcomas and the presence of disease in tumor bed after one were associated with worse five-year LRFS. Tumor bed excision should remain the standard approach, with special consideration to the presence of residual disease.

IntroductionPrimary debulking surgery (PDS), interval debulking surgery (IDS), and platinum-based chemotherapy are the current standard treatments for advanced ovarian cancer (OC). The time to initiation of adjuvant chemotherapy (TTC) could influence patient outcomes.MethodsWe conducted a multicenter retrospective cohort study of advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) OC treated between 2014 and 2018 to assess progression-free survival (PFS) and overall survival (OS) in relation to TTC. All patients underwent a germline multigene panel for BRCA1/2 evaluation.ResultsAmong the 83 patients who underwent PDS, a TTC ≥ 60 days was associated with a shorter PFS (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.04–3.93, p = 0.038), although this association lost statistical significance when adjusting for residual disease (HR 1.52, 95% CI 0.75–3.06, p = 0.244, for TTC and HR 2.73, 95% CI 1.50–4.96, p = 0.001, for residual disease). Among 52 IDS patients, we found no evidence of an association between TTC and clinical outcomes. Ascites, type of chemotherapy, or germline BRCA1/2 mutational status did not influence TTC and were not associated with clinical outcomes in PDS or IDS patients.DiscussionIn conclusion, longer TTC seems to negatively affect prognosis in patients undergoing PDS, especially those with residual disease.