Locally advanced pancreatic cancer (LAPC) represents a unique clinical scenario in which the tumor is considered localized but unresectable due to anatomic factors. Despite a consensus against upfront surgery, no standard approach to induction therapy exists for patients with LAPC. Extended systemic therapy has shown promise in establishing tumor response and remains the standard of care. While associated with improved local control, the timing and role of radiation therapy remain in question. Following adequate response to induction chemotherapy, a safe attempt at margin-negative resection can be considered. Special attention should be given to required vascular skeletonization and/or resection with reconstruction.

OBJECTIVE: Standard neoadjuvant chemotherapy (NACT) for locally advanced esophageal/gastroesophageal junction squamous cancer (LAEGSC), 5-fluorouracil (5FU)+platinum, is toxic and logistically challenging; alternative regimens are needed.
METHODS: Phase III randomized open-label non-inferiority trial at Tata Memorial Center, India, in resectable LAEGSC. Patients were randomized 1:1 to three cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin AUC 6) with paclitaxel 175 mg/m2 (day 1) or 5FU 1000 mg/m2 continuous infusion (days 1-4), followed by surgery.
RESULTS: Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Significantly more patients on paclitaxel + platinum (194 (92.3%)] received all 3 chemotherapy cycles than on 5FU+platinum (170 [85.9%]), P = .009. 5FU + platinum caused more grade ≥ 3 toxicities (124 [69.7%]) than paclitaxel + platinum (97 [51.9%]), P = .001. Surgery was performed in 131 (62.4%) patients on 5FU + platinum vs 139 (66.2%) on paclitaxel + platinum, P = .415. Paclitaxel + platinum resulted in higher pathologic primary tumor clearance (33 [25.8%]) vs 17 [15%]; P = .04), and pathologic complete responses in 21.9% compared to 12.4% from 5FU + platinum, P = .053. Median OS was 27.5 months (95% CI, 18.6-43.5) from paclitaxel + platinum, which was non-inferior to 27.1 months (95% CI, 18.8-40.7) from 5FU + platinum; HR, 0.89 (95% CI, 0.72-1.09); P = .346.
CONCLUSIONS: Neoadjuvant paclitaxel + platinum chemotherapy is safer, and results in similar R0 resections, higher pathologic tumor clearance and non-inferior survival, compared to 5FU + platinum. Paclitaxel + platinum should replace 5FU + platinum as NACT for resectable LAEGSC.
UNASSIGNED: CTRI/2014/04/004516.

BACKGROUND: The use of neoadjuvant therapy (NAT) in distal cholangiocarcinoma (dCCA) with regional arterial or extensive venous involvement, is not widely accepted and evidence is sparse.
OBJECTIVE: To synthesise evidence on NAT for dCCA and present the experience of a high-volume tertiary-centre managing dCCA with arterial involvement.
METHODS: A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received NAT. All patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained database. Baseline characteristics, NAT type, progression to surgery and oncological outcomes were collected.
RESULTS: Twelve studies were included. The definition of \"unresectable\" locally advanced dCCA was heterogenous. Four studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement. R0 resection rate ranged between 0 and 100% but without survival benefit in most cases. Remaining studies considered either NAT in resectable dCCA or inclusive with extrahepatic CCA. The presented case series includes 9 patients (median age 67, IQR 56-74 years, male:female 5:4) referred for NAT for borderline resectable or locally advanced disease. Three patients progressed to surgery and 2 were resected. One patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months post-operatively.
CONCLUSIONS: Evidence for benefit of NAT is limited. Consensus on criteria for uniform definition of resectability for dCCA is required. We propose using the established National-Comprehensive-Cancer-Network® criteria for pancreatic ductal adenocarcinoma.

OBJECTIVE: To evaluate the prevalence and characteristics of different HER2 categories among patients with advanced breast cancer (aBC) and describe treatment patterns and outcomes of those with HER2-low disease.
METHODS: A retrospective cohort study was conducted via chart review at the Huntsman Cancer Institute, including patients diagnosed with aBC (stages IIIB, IIIC and IV) between 2010 and 2019. All patients with IHC1+ were considered HER2-low unless FISH was positive. Patients with IHC2+ were only classified as HER2-low if a negative FISH was documented. The prevalence and characteristics of each HER2 category were reported. Treatment patterns and survival outcomes of HER2-low patients who received first line treatment in 2017 or later were presented.
RESULTS: A total of 240 of 414 patients (58%) with aBC were HER2-low, with the majority of patients (83%) classified as hormone receptor (HR)-positive. In first line, most HR-positive patients received endocrine therapy with chemotherapy for stage IIIB/IIIC (47%) and with CDK4/6 inhibitors for stage IV breast cancer (50%) Most HR-negative patients received chemotherapy alone (92% for stage IIIB/IIIC, 60% for stage IV). In second line, chemotherapy alone was the most common modality (21.4% for HR-positive; 45.5% for HR-negative). Median overall survival was 37.7 months while median progression-free survival from first line was 18.0 months, decreasing to 8.0 months in second line.
CONCLUSIONS: A substantial proportion of patients previously classified as HER2-negative have low but detectable HER2 expression and may benefit from novel HER2-directed agents, which have demonstrated clinical benefit in this population post-chemotherapy.

UNASSIGNED: Thymic epithelial tumors (TETs) are rare and originate from the thymus. Thymomas and thymic carcinomas are the most common types of TETs. Of the two, thymomas tend to have a better prognosis and are typically localized, while thymic carcinomas have a worse prognosis and are more likely to spread. The Masaoka-Koga staging system is commonly used to determine the stage of TETs. Complete resection is the preferred treatment option, but treating locally advanced TETs can be challenging due to the invasion of surrounding structures. In such cases, induction therapy is administered to downstage the tumors and enable complete resection. We conducted this narrative review to evaluate the current progress in induction treatment for locally advanced TETs.
UNASSIGNED: The literature search was performed using PubMed and Web of Science in June 2023. Prospective and retrospective published trials, systemic and narrative reviews, and meta-analyses were included.
UNASSIGNED: Induction chemotherapy is often used as a preoperative treatment for advanced TETs. Platinum and anthracycline-based chemotherapy regimens are commonly used for treating thymoma (response rate, 37-100%), and complete resection is highly common. Treatment with cisplatin and etoposide, carboplatin and paclitaxel, docetaxel and cisplatin have also demonstrated effectiveness, particularly in patients with thymic carcinoma or thymoma who cannot tolerate anthracycline regimens. The emergence of immunotherapy and targeted therapies may provide additional options for the treatment of TETs. Induction radiotherapy, as the sole treatment for TETs, is not widely practiced due to concerns about potential damage to surrounding tissues. However, combining modern radiation techniques with surgery has shown promising results in selected patients. Induction chemoradiotherapy, which combines chemotherapy and radiation, is an emerging approach for treating TETs. Despite the lack of randomized trials comparing chemotherapy with chemoradiotherapy, concurrent chemoradiation with radiation doses of 40-50 Gy is often considered the optimal induction therapy for thymic carcinoma patients or in more advanced special situations, such as great vessel invasion.
UNASSIGNED: Overall, the optimal treatment for locally advanced TETs remains controversial. Induction therapy, including chemotherapy, radiotherapy, or chemoradiotherapy, is administered to downstage tumors and improve resectability. The choice of treatment depends on individual factors such as tumor stage, histology, and overall patient condition. However, further research and well-designed studies are needed to determine the most effective treatment strategies for locally advanced TETs.

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Background: Recent publications underscore the need for updated recommendations addressing less radical surgery for <2 cm tumors, induction chemotherapy, or immunotherapy for locally advanced stages of cervical cancer, as well as for the systemic therapy for recurrent or metastatic cervical cancer. Aim: To summarize the current evidence for the diagnosis, treatment, and follow-up of cervical cancer and provide evidence-based clinical practice recommendations. Methods: Developed according to AGREE II standards, the guidelines classify scientific evidence based on the Agency for Health Technology Assessment and Tariff System criteria. Recommendations are graded by evidence strength and consensus level from the development group. Key Results: (1) Early-Stage Cancer: Stromal invasion and lymphovascular space involvement (LVSI) from pretreatment biopsy identify candidates for surgery, particularly for simple hysterectomy. (2) Surgical Approach: Minimally invasive surgery is not recommended, except for T1A, LVSI-negative tumors, due to a reduction in life expectancy. (3) Locally Advanced Cancer: concurrent chemoradiation (CCRT) followed by brachytherapy (BRT) is the cornerstone treatment. Low-risk patients (fewer than two metastatic nodes or FIGO IB2-II) may consider induction chemotherapy (ICT) followed by CCRT and BRT after 7 days. High-risk patients (two or more metastatic nodes or FIGO IIIA, IIIB, and IVA) benefit from pembrolizumab with CCRT and maintenance therapy. (4) Metastatic, Persistent, and Recurrent Cancer: A PD-L1 status from pretreatment biopsy identifies candidates for Pembrolizumab with available systemic treatment, while triplet therapy (Atezolizumab/Bevacizumab/chemotherapy) becomes a PD-L1-independent option. Conclusions: These evidence-based guidelines aim to improve clinical outcomes through precise treatment strategies based on individual risk factors, predictors, and disease stages.

About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering the infiltration of oncolytic viruses and various therapeutic drugs-such as antibodies, adoptive cell therapy agents, and chemotherapeutic agents-in reaching the tumor site. Recently, a growing emphasis has been placed on targeting major acellular components of tumor stroma, such as hyaluronic acid and collagen, to enhance drug penetration. Oncolytic viruses can be engineered to express proteolytic enzymes that cleave hyaluronic acid and collagen into smaller polypeptides, thereby softening the desmoplastic stroma, ultimately leading to increased viral distribution along with increased oncolysis and subsequent tumor size regression. This approach may offer new possibilities to improve the resectability of patients diagnosed with BR and LA PDAC.

UNASSIGNED: Cervical cancers are mainly caused by an oncogenic HPV. For locally advanced stages, the standard treatment is radio-chemotherapy (RTCT) followed by brachytherapy. Nevertheless, the prognosis remains highly heterogeneous between patients.
UNASSIGNED: We investigated the prognostic value of HPV circulating tumor DNA (ctDNA) in locally advanced cervical cancers alongside that of Squamous Cell Carcinoma Antigen (SCC-A).
UNASSIGNED: This single-center retrospective study included patients treated in curative intent for an IB3 to IVA squamous cell cervical cancer. Quantification of HPV ctDNA in serum collected at diagnosis was performed using a multiplex digital PCR assay for the simultaneous detection of 8 HPV genotypes.
UNASSIGNED: Among the 97 patients included, 76 patients (78.4%) were treated by RTCT, followed by brachytherapy for 57 patients (60%). HPV ctDNA was detected in 59/97 patients at diagnosis (60.8%). This detection was associated with lymph node invasion (p=0.04) but not with tumor stage. A high level of SCC-A at diagnosis was associated with tumor stage (p=0.008) and lymph node invasion (p=0.012). In univariate analysis, better disease-free survival (DFS) was associated with optimal RTCT regimen (p=0.002), exposure to brachytherapy (p=0.0001) and a low SCC-A at diagnosis (continuous analysis, p=0.002). Exploratory analysis revealed that 3/3 patients (100%) whose HPV ctDNA was still detectable at the end of treatment relapsed, while 6/22 patients (27.3%) whose HPV ctDNA was negative at the end of treatment relapsed.
UNASSIGNED: HPV ctDNA detection at diagnosis of locally advanced cervical squamous cell carcinomas is frequent and related to node invasion, but not to DFS. The prognostic value of HPV ctDNA detection after treatment warrants specific studies.

UNASSIGNED: Systematic inflammation is believed to play a crucial role in tumorigenesis and metastasis. This study aims at evaluating the prognostic value of time-series behavior of systematic inflammation-immune status before and after definitive chemoradiotherapy (dCRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC).
UNASSIGNED: The relationship between systematic inflammation-immune score (SIS, defined as pretreatment peripheral platelet count × neutrophil count/lymphocyte count) and the prognosis was tested in a retrospective study of 386 consecutive LA-NSCLC patients (Group A) with pretreatment SIS and 161 patients (Group B) with SIS before and one month after the dCRT.
UNASSIGNED: SIS of 1400 × 109 was found to be an optimal cutoff point to stratify the patients into high (>1400 × 109) and low (≤1400 × 109) SIS groups. Univariate and multivariate analyses revealed that the SIS, whether before or after dCRT, was an independent predictor for overall survival (OS), progress-free survival (PFS), and distant metastasis-free survival (DMFS). High SIS (>1400 × 109) was shown to predict poor 3-year OS (P=0.006, hazard ratio [HR]=2.427), PFS (P=0.001, HR=2.442) and DMFS (P=0.015, HR=2.119). However, SIS was not related to local regional recurrence-free survival in either Group A (P=0.346) or Group B (P=0.486). Further, the area under the receiver operating characteristic curve of the SIS for OS was higher than the neutrophil count/lymphocyte count ratio, platelet count/lymphocyte count ratio, and other conventional clinic-pathological indices.
UNASSIGNED: The SIS is a stable and more sensitive survival predictor than other inflammation-based factors and conventional clinical indices, which may aid in more accurately stratifying patients for risk assessment and treatment decisions.