Head and neck squamous cell carcinoma (HNSC) is one of most common malignancies with high mortality worldwide. Importantly, the molecular heterogeneity of HNSC complicates the clinical diagnosis and treatment, leading to poor overall survival outcomes. To dissect the complex heterogeneity, recent studies have reported multiple molecular subtyping systems. For instance, HNSC can be subdivided to four distinct molecular subtypes: atypical, basal, classical, and mesenchymal, of which the mesenchymal subtype is characterized by upregulated epithelial-mesenchymal transition (EMT) and associated with poorer survival outcomes. Despite a wealth of studies into the complex molecular heterogeneity, the regulatory mechanism specific to this aggressive subtype remain largely unclear. Herein, we developed a network-based bioinformatics framework that integrates lncRNA and mRNA expression profiles to elucidate the subtype-specific regulatory mechanisms. Applying the framework to HNSC, we identified a clinically relevant lncRNA LNCOG as a key master regulator mediating EMT underlying the mesenchymal subtype. Five genes with strong prognostic values, namely ANXA5, ITGA5, CCBE1, P4HA2, and EPHX3, were predicted to be the putative targets of LNCOG and subsequently validated in other independent datasets. By integrative analysis of the miRNA expression profiles, we found that LNCOG may act as a ceRNA to sponge miR-148a-3p thereby upregulating ITGA5 to promote HNSC progression. Furthermore, our drug sensitivity analysis demonstrated that the five putative targets of LNCOG were also predictive of the sensitivities of multiple FDA-approved drugs. In summary, our bioinformatics framework facilitates the dissection of cancer subtype-specific lncRNA regulatory mechanisms, providing potential novel biomarkers for more optimized treatment of HNSC.

UNASSIGNED: To analyze long-term oncological outcome after 2nd conservative treatment (2ndCT) for patients with ipsilateral 2nd ipsilateral breast tumor event (2ndIBTE).
UNASSIGNED: In this retrospective observational study (N°F20210402152843), patients with 2ndIBTE underwent 2ndCT (lumpectomy + tumor bed re-irradiation). 3rdIBTE (3rdIBTE-FS), regional relapse- (RRFS) and metastatic disease- (MD-FS) free survivals as well as disease-free (DFS), specific (SS) and overall (OS) survival were analyzed. Late toxicity was reported.
UNASSIGNED: Between 09/2000 and 04/2022, 244 patients presented a 2ndIBTE and underwent a 2ndCT. Among them, 113 pts with a minimum follow-up of 60 months were analyzed. Median time interval between 1st and 2ndIBTE was 13.5 years [2-35]. Median 2ndIBTE age was 66.2 years [31-85]. 2ndIBTE were adenocarcinomas (77 %). Tumor size was < 20 mm (86.7 %). 2ndIBTE were grade 1/2 (75 %), with positive hormonal receptor (85 %) and clear surgical margins (no ink on tumor, 90.3 %). In the APBI classification, 21 pts were high-risk (18.6 %), while 77 % were Luminal A/BHer2-. With a MFU of 121.5 months [CI95% 111.7-129.6], 10-year 3rdIBTE-FS was 89 % [83-96]. Then-year RRFS, MDFS, DFS, SS and OS were 94 % [89-100], 89 % [83-96], 78 % [70-87], 95 % [91-100] and 94 % [90 -99] respectively. In multivariate analysis, APBI classification (high-risk; HR2.66 [1.01-7.1], p = 0.049) and tumor size (≥20 mm; HR2.64 [1.02-6.8], p = 0.045) were considered independent prognostic factors for DFS.Ninety-seven late complications were observed (fibrosis 64 %) with 6.2 % G ≥ 3 late toxicity. Cosmetic outcome was excellent/good in 91.2 %.
UNASSIGNED: With long follow-up, 2ndIBTE managed with 2ndCT allows second breast preservation without oncological outcome compromise and acceptable G ≥ 3 toxicity.

UNASSIGNED: To report the results of the Single Fraction Early Prostate Irradiation (SiFEPI) phase 2 prospective trial.
UNASSIGNED: The SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and favorable-intermediate (FIR) risk prostate cancers. After rectal spacer placement, a single fraction of 20 Gy was delivered to the prostate. Oncological outcome (biochemical (bRFS) and local (lRFS) relapses, disease-free (DFS) and overall (OS) survivals and toxicity (acute/late genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities were investigated.
UNASSIGNED: From 03/2014 to 10/2017, 35 pts were enrolled, of whom 33 were evaluable. With a median age of 66 y [46-79], 25 (76 %) and 8 (24 %) pts were LR and FIR respectively. With a MFU of 72.8 months [64-86], 6y-bRFS, lRFS and mRFS were 62 % [45-85], 61 % [44-85] and 93 % [85-100] respectively while 6y-DFS, CSS and OS were 54 % [37-77], 100 % and 89 % [77-100] respectively. Late GU, GI and S toxicities were observed in 11 pts (33 %;18G1), 4 pts (12 %;4G1) and 7 pts (21 %;1G1,5G2,1G3) respectively. Biochemical relapse (BR) was observed in 11 pts (33 %;7LR,4FIR) with a median time interval between HDB and BR of 51 months [24-69]. Nine of these pts (82 %) presented a histologically proven isolated local recurrence.
UNASSIGNED: Long-term results of the SiFEPI trial show that a single fraction of 20 Gy leads to sub-optimal biochemical control for LR/FIR prostate cancers. The late GU and GI toxicity profile is encouraging, leading to consideration of HDB as a safe irradiation technique.

UNASSIGNED: Treatment for stage IIIA N2 non-small cell lung cancer (NSCLC) typically involves a combination of chemotherapy, radiotherapy, and surgery, but the optimal sequencing is not determined. Local recurrence rates following surgery remain high, and the role of postoperative radiotherapy (PORT) in N2 disease is unclear. This meta-analysis aims to determine whether PORT provides additional survival advantage beyond observation for patients with stage IIIA N2 disease who have undergone complete surgical resection and received adjuvant chemotherapy.
UNASSIGNED: All studies comparing adjuvant chemotherapy and PORT versus adjuvant chemotherapy alone after curative surgical resection for stage IIIA N2 NSCLC were included. Meta-analysis was performed using random effects modelling in accordance with MOOSE (Meta-Analyses and Systematic Reviews of Observational Studies) guidelines. Subgroup analysis, heterogeneity, and risk of bias were assessed, with meta-regression to determine the effects of patient and tumor characteristics on outcomes.
UNASSIGNED: Ten studies with a pooled dataset of 18,077 patients (5453 PORT, 12,624 no PORT) were included. PORT significantly improved both overall survival (OS) and disease-free survival (DFS) at 1 year (OS: hazard ratio [HR], 0.768; DFS: HR, 0.733), 3 years (OS: HR, 0.914; DFS: HR, 0.732), and 5 years (OS: HR, 0.898; DFS: HR, 0.735, all P < .0001). These effects were independent of specific patient or tumor characteristics.
UNASSIGNED: This study demonstrates a significant DFS and OS benefit from the addition of PORT following adjuvant chemotherapy. We advocate the consideration of PORT for such patients following specialist multidisciplinary assessment and comprehensive discussion of the benefits and risks of treatment.

UNASSIGNED: To analyze the oncological outcome in elderly (>70 years) prostate cancer after high-dose rate brachytherapy (HDB) boost.
UNASSIGNED: In this retrospective study, patients with intermediate (IR) and high-risk (HR) prostate cancer underwent external beam radiation therapy (EBRT) followed by HDB boost with/without androgen deprivation therapy (ADT). The impact of age (≤70y vs. > 70y) was investigated. Oncological outcome focused on biochemical relapse-free survival (bRFS), cause-specific (CSS) and overall survival (OS). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were investigated.
UNASSIGNED: From 07/08 to 01/22, 518 pts received a HDB boost, and 380 were analyzed (≤70y:177pts [46.6%] vs. > 70y:203pts [53.4%]). Regarding NCCN classification, 98 pts (≤70y: 53pts; >70y: 45pts; p = 0.107) and 282 pts (≤70y: 124pts; >70y: 158pts; p = NS) were IR and HR pts respectively. Median EBRT dose was 46 Gy [37.5-46] in 23 fractions [14-25]. HDB boost delivered a single fraction of 14/15 Gy (79%). ADT was used in 302 pts (≤70y: 130pts; >70y: 172pts; p = 0.01). With MFU of 72.6 months [67-83] for the whole cohort, 5-y bRFS, 5-y CSS and 5-y OS were 88% [85-92], 99% [97-100] and 94% [92-97] respectively; there was no statistical difference between the two age groups except for 5-y CSS (p = 0.05). Late GU and GI toxicity rates were 32.4% (G ≥ 3 7.3%) and 10.1% (no G3) respectively.
UNASSIGNED: For IR and HR prostate cancers, HDB boost leads to high rates of disease control with few late G ≥ 3 GU/GI toxicities. For elderly pts, HDB boost remains warranted mainly in HR pts, while competing comorbidity factors influence OS.

UNASSIGNED: Recent advances in the treatment algorithm of locally advanced rectal cancer (LARC) have significantly improved complete response (CR) rates and disease-free survival (DFS), but therapy resistance, with its substantial impact on outcomes and survival, remains a major challenge. Our group has recently unraveled a critical role of interleukin-1α (IL-1α) signaling in activating inflammatory cancer-associated fibroblasts (iCAFs) and mediating radiation-induced senescence, extracellular matrix (ECM) accumulation, and ultimately therapy resistance. We here summarize the recently initiated ACO/ARO/AIO-21 phase I trial, testing the IL-1 receptor antagonist (IL-1 RA) anakinra in combination with fluoropyrimidine-based chemoradiotherapy (CRT) for advanced rectal cancer.
UNASSIGNED: The ACO/ARO/AIO-21 is an investigator-driven, prospective, open-labeled phase I drug-repurposing trial assessing the maximum tolerated dose (MTD) of capecitabine administered concurrently to standard preoperative radiotherapy (45 Gy in 25 fractions followed by 9 Gy boost in 5 fractions) in combination with fixed doses of the IL1-RA anakinra (100 mg, days -10 to 30). Capecitabine will be administered using a 3 + 3 dose-escalation design (500 mg/m2 bid; 650 mg/m2 bid; 825 mg/m2 bid, respectively) from day 1 to day 30. Response assessment including digital rectal examination (DRE), endoscopy and pelvic magnetic resonance imaging (MRI) is scheduled 10 weeks after completion of CRT. For patients achieving clinical complete response (cCR), primary non-operative management is provided. In case of non-cCR immediate total mesorectal excision (TME) will be performed. Primary endpoint of this phase I trial is the MTD of capecitabine.
UNASSIGNED: Based on extensive preclinical research, the ACO/ARO/AIO-21 phase I trial will assess whether the IL-1RA anakinra can be safely combined with fluoropyrimidine-based CRT in rectal cancer. It will further explore the potential of IL-1 inhibition to overcome therapy resistance and improve response rates. A comprehensive translational research program will expand our understanding from a clinical perspective and may help translate the results into a randomized phase II trial.

The incidence of adenocarcinoma of the cervix in pregnancy is exceptionally rare, and thus there is no consensus on its management. Here, we report two cases of adenocarcinoma of the cervix diagnosed in the context of pregnancy. In our first case, a patient referred to colposcopy for atypical glandular cells of undetermined significance was subsequently diagnosed with well differentiated endocervical adenocarcinoma on cone biopsy. Just prior to the cone biopsy, she was incidentally found to have a first trimester pregnancy loss. The patient subsequently underwent a radical hysterectomy and bilateral sentinel lymph node dissection. Final pathology revealed a stage 1B1 (FIGO 2009) well differentiated adenocarcinoma of the cervix. Interestingly, the tumour was positive for estrogen receptor, which is unusual for cervical adenocarcinoma. In our second case, a patient presented with a pedunculated, exophytic cervical neoplasm at 31 weeks GA with self-limiting antepartum hemorrhage. The primary lesion measured 52 mm in diameter on MRI and was amputated at the base during the patient\'s elective repeat cesarean section. Final pathology revealed a stage IB2 (FIGO 2009) mucinous adenocarcinoma of the cervix. The patient subsequently underwent a radical hysterectomy and bilateral pelvic lymph node dissection 17 weeks after initial presentation. The depth of invasion was 2.2 mm, restricted to the inner third of the cervical wall, and there was no lymphovascular space invasion in the surgical specimen. Surgical margins, parametria, and lymph nodes were all negative for adenocarcinoma. This tumour was also found to be estrogen receptor/progesterone receptor (ER/PR) positive, again unusual for cervical adenocarcinoma. P16 was strongly positive and HPV DNA studies were also positive for human papilloma virus 18. The patient received adjuvant external beam radiotherapy to the pelvis and currently remains in remission.

UNASSIGNED: Hepatocellular carcinoma (HCC) has variable etiological risk factors. Radiofrequency ablation (RFA) and surgical resection (SR) are frequently used as curative treatment options. In the present study, we assessed the etiological factors and efficacy of RFA and SR in patients with unifocal HCC in a real-life setting.
UNASSIGNED: Of 870 patients with HCC seen over a period of nine years, 785 patients were assessed for stage and etiological risk factors. Of these, 110 (14%) patients with single HCC who were either treated with RFA (n = 72) or SR (n = 38) were evaluated for their outcomes in terms of overall survival (OS) and disease-free survival (DFS) over 3 years.
UNASSIGNED: Of 785 patients [median age 60 (range 51-65) years, males (n = 685, 87.3%)] with HCC, viral hepatitis [HBV and HCV with or without alcohol = 502 (63.9%)] was the most common etiology; nonalcoholic steatohepatitis (NASH) and alcohol as an etiology showed increase over the years. About 677 (86.2%) patients had evidence of cirrhosis; NASH and HBV were predominant causes in noncirrhotic patients. Even though the groups were not matched, in 110 patients subjected to either RFA [mean tumor size, 2.2 (1.9-2.8) cm] or SR [mean tumor size, 7.1 (4.8-9.7) cm], tumor progression was observed in 49 (68%) and 16 (42%) patients in RFA and SR groups, respectively, with superior DFS in the SR group (P < 0.01). Of total 31 deaths, 20 (27.8%) deaths were in the RFA group and 11 (28.9%) in the SR group with no difference in OS at 3 years.
UNASSIGNED: Viral hepatitis with or without alcohol is the commonest etiological factor for HCC in Northern India; NASH and alcohol are increasing over the years. In a real-life setting, in patients with unifocal HCC, there is no difference in overall 3-year survival subjected to SR or RFA with better DFS in the SR group.

MicroRNA (miRNA) deregulation plays a critical role in the heterogeneous development of prostate cancer (PCa) by tuning mRNA levels. Herein, we aimed to characterize the molecular features of PCa by clustering the miRNA-regulated transcriptome with non-negative matrix factorization. Using 478 PCa samples from The Cancer Genome Atlas, four molecular subtypes (S-I, S-II, S-III, and S-IV) were identified and validated in two merged microarray and RNAseq datasets with 656 and 252 samples, respectively. Interestingly, the four subtypes showed distinct clinical and biological features after comprehensive analyses of clinical features, multiomic profiles, immune infiltration, and drug sensitivity. S-I is basal/stem/mesenchymal-like and immune-excluded with marked transforming growth factor β, epithelial-mesenchymal transition and hypoxia signals, increased sensitivity to olaparib, and intermediate prognosis. S-II is luminal/metabolism-active and responsive to androgen deprivation therapy with frequent TMPRSS2-ERG fusion and a good prognosis. S-III is characterized by moderate proliferative and metabolic activity, sensitivity to taxane-based chemotherapy, and intermediate prognosis. S-IV is highly proliferative with moderate EMT and stemness, frequent deletions of TP53, PTEN and RB, and the poorest prognosis; it is also immune-inflamed and sensitive to anti-PD-L1 therapy. Overall, based on miRNA-regulated gene profiles, this study identified four distinct PCa subtypes that could improve risk stratification at diagnosis and provide therapeutic guidance.

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue malignant tumor. Treatment of RMS usually includes primary tumor resection along with systemic chemotherapy. Two-dimensional (2D) cell culture systems and animal models have been extensively used for investigating the potential efficacy of new RMS treatments. However, RMS cells behave differently in 2D culture than in vivo, which has recently inspired the adoption of three-dimensional (3D) culture environments. In the current paper, we will describe the detailed methodology we have developed for fabricating a 3D engineered model to study alveolar RMS (ARMS) in vitro. This model consists of a thermally cross-linked collagen disk laden with RMS cells that mimics the structural and bio-chemical aspects of the tumor extracellular matrix (ECM). This process is highly reproducible and produces a 3D engineered model that can be used to analyze the cytotoxicity and autophagy induction of drugs on ARMS cells. The most improtant bullet points are as following:•We fabricated 3D model of ARMS.•The current ARMS 3D model can be used for screening of chemotherapy drugs.•We developed methods to detect apoptosis and autophagy in ARMS 3D model to detect the mechansims of chemotherapy agents.