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A multimodality approach, which usually includes chemotherapy, surgery, and/or radiotherapy, is optimal for patients with localized pancreatic cancer. The timing and sequence of these interventions depend on anatomic resectability and the biological suitability of the tumor and the patient. Tumors with vascular involvement (ie, borderline resectable/locally advanced) require surgical reassessments after therapy and participation of surgeons familiar with advanced techniques. When indicated, venous reconstruction should be offered as standard of care because it has acceptable morbidity. Morbidity and mortality of pancreas surgery may be mitigated when surgery is performed at high-volume centers., Competing Interests: Disclosure A.C. Wei received institutional clinical trial funding from IPSEN pharmaceuticals. M. Liu has no relevant conflicts of interest to report. Memorial Sloan Kettering has institutional financial interests relative BioNTech, Epistem Prognostics, Clarity Pharmaceuticals., (Copyright © 2024 Elsevier Inc. All rights reserved.)

• Never smokers have significantly better overall survival after chemoradiotherapy for locally-advanced non-small-cell lung cancer. • Never smokers have better progression-free survival after chemoradiotherapy for locally-advanced non-small-cell lung cancer. • Never smokers with lung cancer have better overall survival irrespective of actionable tumour mutation status. Smoking is a risk factor for the development of lung cancer and reduces life expectancy within the general population. Retrospective studies suggest that non-smokers have better outcomes after treatment for lung cancer. We used a prospective database to investigate relationships between pre-treatment smoking status and survival for a cohort of patients with stage III non-small-cell lung cancer (NSCLC) treated with curative-intent concurrent chemoradiotherapy (CRT). All patients treated with CRT for stage III NSCLC at a major metropolitan cancer centre were prospectively registered to a database. A detailed smoking history was routinely obtained at baseline. Kaplan-Meier statistics were used to assess overall survival and progression-free survival in never versus former versus current smokers. Median overall survival for 265 eligible patients was 2.21 years (95 % Confidence Interval 1.78, 2.84). It was 5.5 years (95 % CI 2.1, not reached) for 25 never-smokers versus 1.9 years (95 % CI 1.5, 2.7) for 182 former smokers and 2.2 years (95 % CI 1.3, 2.7) for 58 current smokers. Hazard ratio for death was 2.43 (95 % CI 1.32–4.50) for former smokers and 2.75 (95 % CI 1.40, 5.40) for current smokers, p = 0.006. Actionable tumour mutations (EGFR, ALK, ROS1) were present in more never smokers (14/25) than former (9/182) or current (3/58) smokers. TKI use was also higher in never smokers but this was not significantly associated with superior survival (Hazard ratio 0.71, 95 % CI 0.41, 1.26). Never smokers have substantially better overall survival than former or current smokers after undergoing CRT for NSCLC. [ABSTRACT FROM AUTHOR]

SBRT was feasible for approximately half of the locally-advanced NSCLC patients we assessed and for these patients has the potential to reduce a 30 fraction course to 12 fractions. Using SBRT in this setting requires compromises in techniques and further compromises may allow SBRT in a greater proportion of patients.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of early and locally-advanced non-small-cell lung cancer (NSCLC) was published in 2017, and covered the diagnosis, staging, management and treatment of both early stage I and II disease and locally-advanced stage III disease. At the ESMO Asia Meeting in November 2018, it was decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the ESMO 2017 guidelines to take into account potential differences related to ethnicity, cancer biology and standard practices associated with the treatment of locally-advanced, unresectable NSCLC in Asian patients. These guidelines represent the consensus opinions reached by those experts in the treatment of patients with lung cancer who represented the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and it was independent of both local current treatment practices and the treatment availability and reimbursement situations in the individual participating Asian countries. [ABSTRACT FROM AUTHOR]

OBJECTIVE In China, vinorelbine plus an anthracycline is a common neoadjuvant regimen for locally-advanced breast cancer (LABC). Pegylated liposomal doxorubicin (PLD) is an alternate anthracycline formulation with a more favorable safety profi le compared with conventional anthracyclines. METHODS In this open-label trial, 61 women with LABC received up to 6 cycles of PLD 30 mg/m2 on Day 1 and vinorelbine 25 mg/m2 on Days 1 and 8 every 21 days. Hormone receptor and/or HER2 status was not routinely available. RESULTS The overall clinical response rate (primary efficacy endpoint) was 80% (95% CI: 68%-89%). Two patients achieved a pathological complete response (3%), with 75% having their tumor down-staged, and 89% proceeding to tumor resection. The most frequent nonhematologic adverse events were stomatitis, fever, rash, and palmar-plantar erythrodysesthesia, with none considered serious. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 10% and 2% of patients, respectively. CONCLUSION PLD plus vinorelbine demonstrated comparable efficacy to conventional anthracyclines plus vinorelbine in the neoadjuvant treatment of LABC, but may offer safety advantages.

Background: Perioperatory chemoradiotherapy (CRT) improves local control and survival in patients with locally advanced rectal cancer (LARC). The objective of the current study was to evaluate the addition of bevacizumab (BEV) to preoperative capecitabine (CAP)-based CRT in LARC, and to explore biomarkers for downstaging. Methods: Patients (pts) were randomized to receive 5 weeks of radiotherapy 45 Gy/25 fractions with concurrent CAP 825 mg/m² twice daily 5 days per week and BEV 5 mg/kg once every 2 weeks (3 doses) (arm A), or the same schedule without BEV (arm B). The primary end point was pathologic complete response (ypCR: ypT0N0). Results: Ninety pts were included in arm A (44) or arm B (46). Grade 3-4 treatment-related toxicity rates were 16% and 13%, respectively. All patients but one (arm A) proceeded to surgery. The ypCR rate was 16% in arm A and 11% in arm B (p =0.54). Fifty-nine percent vs 39% of pts achieved T-downstaging (arm A vs arm B; p =0.04). Serial samples for biomarker analyses were obtained for 50 out of 90 randomized pts (arm A/B: 22/28). Plasma angiopoietin-2 (Ang-2) levels decreased in arm A and increased in arm B (p <0.05 at all time points). Decrease in Ang-2 levels from baseline to day 57 was significantly associated with tumor downstaging (p =0.02). Conclusions: The addition of BEV to CAP-based preoperative CRT has shown to be feasible in LARC. The association between decreasing Ang-2 levels and tumor downstaging should be further validated in customized studies. Trial registry: Clinicaltrials.gov identifier NCT01043484. Trial registration date: 12/30/2009. [ABSTRACT FROM AUTHOR]

Background: To evaluate whether the addition of bevacizumab (BVZ) to capecitabine-based chemoradiotherapy in the preoperative treatment of locally advanced rectal cancer (LARC) improves efficacy measured by the pathological complete response (pCR) rate. Methods: A phase II two-step design was performed. Patients received four cycles of therapy consisting of: BVZ 10 mg/kg in first infusion on day 1 and 5 mg/kg on days 15, 29, 43, capecitabine 1800 mg/m2/day 5 days per week during radiotherapy, which consisted of external-beam irradiation (45 Gy in 1.8 Gy dose per session over 5 sessions/ week for 5 weeks). Six to eight weeks after completion of all therapies surgery was undergone. To profile the biological behaviour during BVZ treatment we measured molecular biomarkers before treatment, during BVZ monotherapy, and during and after combination therapy. Microvessel density (MVD) was measured after surgery. Results: Forty-three patients were assessed and 41 were included in the study. Three patients achieved a pathological complete response (3/40: 7.5%) and 27 (67.5%) had a pathological partial response, (overall pathological response rate of 75%). A further 8 patients (20%) had stable disease, giving a disease control rate of 95%. Downstaging occurred in 31 (31/40: 77.5%) of the patients evaluated. This treatment resulted in an actuarial 4-year disease-free and overall survival of 85.4 and 92.7% respectively. BVZ with chemoradiotherapy showed acceptable toxicity. No correlations were observed between biomarker results and efficacy variables. Conclusion: BVZ with capecitabine and radiotherapy seem safe and active and produce promising survival results in LARC. Trial registration: ClinicalTrials.gov Identifier NCT00847119. Trial registration date: February 18, 2009. [ABSTRACT FROM AUTHOR]

Objective To describe the survival benefit associated with radical prostatectomy ( RP), as compared with initial observation, in patients with locally advanced prostate cancer ( PCa). Patients and Methods Overall, 1382 patients with locally advanced PCa treated with RP or initial observation between 1995 and 2009 were identified from the Surveillance, Epidemiology and End Results Medicare insurance programme-linked database. Patients were matched using propensity-score methodology, then 10-year cancer-specific mortality ( CSM) rates were estimated and the number needed to treat ( NNT) was calculated. Competing-risks regression analyses tested the relationship between treatment type and CSM. Results Overall, the 10-year CSM rates were 11.8 and 19.3% for patients treated with RP and initial observation, respectively ( P < 0.001). The corresponding 10-year NNT was 13. The 10-year CSM rates for the same treatment groups were 8.9 vs 13.9%, respectively, for Gleason score ≤7, 16.8 vs 27.8%, respectively, for Gleason score 8-10, 10.1 vs 15.8%, respectively, for clinical stage T3a, and 17.0 vs 29.3%, respectively, for T3b/ T4, respectively (all P ≤ 0.04). The corresponding NNTs were 20, 9, 17 and 8, respectively. In multivariable analyses, RP was an independent predictor of more favourable CSM rates in all categories (all P ≤ 0.04). In separate sensitivity analyses, no differences were recorded when patients treated with radiotherapy were compared with those receiving RP ( P = 0.4). Conversely, patients undergoing initial observation had a higher risk of CSM compared with those treated with radiotherapy ( P = 0.03). Conclusions RP leads to a significant survival advantage compared with observation in patients with locally advanced disease. The highest benefit was observed in patients with T3b/ T4 and Gleason score 8-10 disease. [ABSTRACT FROM AUTHOR]

Introduction : Surgical resection is the only curative treatment for gastric cancer. However, the overall prognosis of gastric adenocarcinoma is poor and advanced disease may even make surgical treatment impossible. It has been theoretically proposed that administration of chemotherapy before surgical resection may down-stage the disease state and facilitate resectability especially in locally-advanced tumors. Aim : We wanted to assess the effect of administration of neoadjuvant chemotherapy on tumor resectability in patients with locally-advances gastric adenocarcinoma. Materials and methods : During a randomized-controlled trial, we divided 60 patients with locally-advanced gastric adenocarcinoma into two groups of neoadjuvant chemotherapy and surgery (case) versus surgery alone (control). Because of patient dropouts, we analyzed the results for 22 and 29 patients in case and control groups respectively. The study period was March 21, 2011 to March 20, 2014. A non-randomized set of 23 patients were also added to the control group (Multi-center analysis). The analysis was repeated for non-randomized patients (22 case patients versus 52 control patients). Results : The mean age of patients in case and control groups was 58.3 ± 9.1 and 59.7 ± 8.7 years of age respectively ( p > 0.05). Male to female ratio was 15/7 and 41/11 in case and control groups respectively ( p > 0.05). In Randomized patients, 19 patients (86.4%) were resectable in case group; while 16 patients (55.2%) were resectable in control group ( p < 0.05). Multicenter analysis also revealed resectability in 19 patients (86.4%) and 31 patients (59.6%) of case and control groups respectively ( p < 0.05). Conclusion : We conclude that neoadjuvant chemotherapy could increase tumor resectability rate in patients with locally-advanced gastric adenocarcinoma. However, further studies are necessary to confirm the effect of this modality on patients' overall survival. [ABSTRACT FROM AUTHOR]

Objectives Although the standard treatment for patients with stage IIIA non-small cell lung cancer (NSCLC) is chemoradiotherapy, some patients are considered for trimodality therapy [TT]. We analyzed outcomes for stage IIIA NSCLC, treated with TT and compared them with concurrent chemoradiotherapy [con-CRT]. Materials and methods Patients treated between January 2007 and December 2011 were retrospectively analyzed. Not included were patients with sulcus superior tumors, unknown T/N-status, or recurrent disease after con-CRT followed by surgery. All patients were discussed at our multidisciplinary thoracic tumor board (MTB). Results Mean Charlson Comorbidity Index was 2 for TT and con-CRT patients. TT patients were younger (median TT=56 years vs. con-CRT=62 years; p=0.001) and had less advanced cN-stage (TT cN2=41% vs. 83% for CRT; p<0.001). 44% of TT patients had T4-stage vs. 12% of con-CRT patients. Median RT dose was lower for TT (50Gy vs. 66Gy; p=0.001) and median RT planning target volume (PTV) in TT and con-CRT patients was 525cm³ and 655cm³ (p=0.010), respectively. The majority of TT patients had a lobectomy (23/32). Median follow-up was 30.3 months (95% CI=18.7-41.9) for TT and 51 months (95% CI=24.9-77.4) for con-CRT. Median overall survival was not reached for TT and was 18.6 months (95% CI=12.8-24.4) for con-CRT (p=0.001). For PTV

Background: Some surgeons remain hesitant to perform immediate breast reconstruction (IBR) in patients with higher risk cancers owing to concerns about cancer recurrence and/or detection. Our objective was to determine the rate of ipsilateral local-regional recurrence for stage II/III patients who underwent IBR., Methods: The National Cancer Database special study mechanism was used to create a stratified sample of women diagnosed with stage II/III breast cancer from 1217 facilities. Demographic, tumor, and recurrence data for women who underwent mastectomy with or without IBR were abstracted, including location of recurrence and method of detection. Estimates of 5-year local-regional recurrence rates were calculated and factors associated with recurrence were identified with multivariable Cox regression., Results: Some 13% (692/5318) of stage II/III patients underwent IBR after mastectomy. Patients undergoing IBR were younger (P < .001), with fewer comorbid conditions (P < .001), and with lower tumor burden in the breast (P = .001) and the lymph nodes (P = 0.01). The 5-year rate of ipsilateral local-regional recurrence was 3.6% with no significant difference between patients with or without IBR (3.0% vs. 3.7%, P = .4). Most recurrences were detected by the patient (45%) or on physician examination (24%). Reconstruction was not associated with recurrence on multivariable analysis (hazard ratio = 0.83, P = .52)., Conclusion: Women with stage II/III breast cancer selected for IBR had similar rates of ipsilateral local-regional recurrence compared with those undergoing mastectomy alone. Offering IBR after mastectomy in a patient-centered manner to select patients with stage II/III breast cancer is an acceptable consideration., (Copyright © 2021. Published by Elsevier Inc.)

Objective : To determine whether adjuvant chemotherapy (ACH) influences cancer-specific mortality, bladder cancer-specific mortality, and other-cause mortality in patients with locally advanced upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU) through the use of competing risk analysis. Methods : Among 785 patients with UTUC who underwent RNU from 1994 through 2015, we analyzed 338 individuals with locally advanced UTUC (pathologic T3-T4 and/or positive lymph nodes) without distant metastases. Patients were classified into two groups according to receipt of ACH. We performed a 1:1 propensity score-matching analysis between the ACH and no ACH group. The study endpoints were UTUC- and other cause-specific survivals. The association of potential risk factors with outcome was tested with the Fine and Gray regression model. Results : During a median follow-up duration of 31.5 months, rates of UTUC- and other cause-mortalities were 32.9% (n = 79) and 8.7% (n = 21), respectively. Of note, there were no significant differences in overall survival between the observation and ACH groups according to the competing risks of death (UTUC and other causes of death). Multivariate analysis showed that only older age at surgery (≥ 65 years; hazard ratio [HR] = 1.73), multifocality (HR = 1.74), and tumor size (HR = 1.92) remained as poor predictors of UTUC-specific survival. Additionally, positive surgical margin was only identified as independent predictor of other causes of death (HR = 4.23). Conclusion : In summary, postoperative chemotherapy failed to improve UTUC- and other cause-specific survival rates, based on competing risk analysis after propensity score-matching., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background Patients with locally advanced prostate cancer (PCa) have worse outcomes after radical prostatectomy (RP) than patients with more favorable parameters. We conducted a phase II study of neoadjuvant chemotherapy with docetaxel before RP during 2000 to 2003 in patients with locally advanced disease. We report an updated long-term survival analysis of these patients. Material and methods Overall, 28 patients with locally advanced PCa (defined as serum preoperative [initial] prostate-specific antigen level≥15 ng/ml, clinical≥T2b disease, or biopsy Gleason score ≥8) and no evidence of metastatic disease received 6 weekly doses of intravenous docetaxel (40 mg/m 2 ) followed by RP. Disease status was assessed by shared medical records or followed by phone and fax. Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen level readings≥0.2 ng/ml. A Social Security Death Index search was conducted on all patients to ascertain date of death if unavailable in records. Results In total, 28 patients completed chemotherapy and underwent RP. At a median follow-up of 130 months (range: 37–166 mo), 10 patients (36%) remained alive and disease free clinically and biochemically with no additional therapy, whereas 18 patients (64%) had BCR. The estimated 10-year BCR-free survival is 33.5%, metastasis-free survival is 68.7%, PCa-specific survival is 92.2%, and overall survival is 79.7%. Conclusions The use of neoadjuvant docetaxel chemotherapy in patients with locally advanced PCa undergoing RP remains undefined. Results from this study are informative but only hypothesis generating given the study was not powered for survival. Mature data from the ongoing CALGB 90203 and GETUG-12 studies will shed light on this clinical question. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is among the top 5 most common cancers worldwide, but is particularly devastating due to its insidious nature. Complete surgical resection remains the only potential curative treatment, although only 20 % of patients present with a resectable tumor. Patients may alternatively present with borderline resectable pancreatic cancer or locally advanced pancreatic cancer and can be offered treatment with neoadjuvant intent. The effectiveness of these treatments is unclear and there is a paucity of data to suggest one optimal treatment approach., Case Presentation: We describe a 61-year-old female who presented with a two-week history of obstructive jaundice in the context of vague abdominal pain that had been ongoing for years prior to her visit. CT scan of the abdomen confirmed a hypovascular mass in the uncinate process consistent with borderline resectable pancreatic cancer. Pancreatic adenocarcinoma was confirmed with endoscopic ultrasound guided fine-needle aspiration cytology. Following multidisciplinary discussion, it was recommended that she undergo treatment with FOLFIRINOX. After a total of 13 cycles, follow up CT revealed that the lesion had decreased in size and she was offered resection as a potentially curative treatment. She underwent pancreaticoduodenectomy. Final pathology report revealed no evidence of residual adenocarcinoma (ypT0 ypN0 (0/23)). The patient remains disease-free 15 months following surgery., Conclusion: To date, there have been very few reports of a complete pathological response following neoadjuvant therapy in borderline resectable or locally advanced pancreatic cancer. This report describes a unique case of a complete pathological remission in a patient with borderline resectable pancreatic cancer following FOLFIRINOX therapy alone and adds to the growing base of evidence meriting the initiation of clinical trials to assess the efficacy of FOLFIRINOX in these subsets of pancreatic cancer.