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BACKGROUND - Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection.
METHODS - We reviewed patients with resected HC between 2000 and 2015 from the ten institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium. We analyzed the impact of AT on RFS and OS. The probability of RFS and OS were calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis.
RESULTS - A total of 249 patients underwent curative resection for HC. Patients who received AT and those who did not had similar demographic and preoperative features. In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.58, P = 0.013), and this was maintained in a propensity matched analysis (HR 0.66, P = 0.033). The protective effect of AT remained significant when node negative patients were excluded (HR 0.28, P = 0.001), while it disappeared (HR 0.76, P = 0.260) when node positive patients were excluded.
CONCLUSIONS - AT should be strongly considered after curative-intent resection for HC, particularly in patients with node positive disease.
© 2017 Wiley Periodicals, Inc.
BACKGROUND - A subset of patients with rectal cancer who undergo neoadjuvant chemoradiation therapy will develop a complete pathologic tumor response. Complete nodal response is not universal in these patients and is difficult to assess clinically. Quantifying the risk of nodal disease would allow for targeted therapy with either radical resection or "watchful waiting."
OBJECTIVE - This study aimed to identify risk factors for residual nodal disease in ypT0 rectal adenocarcinoma.
DESIGN - This is a retrospective case control study.
SETTINGS - The National Cancer Database 2006 to 2014 was used to identify patients for this study.
PATIENTS - Patients with stage II/III rectal adenocarcinoma who completed chemoradiation therapy followed by resection and who had ypT0 tumors were included. Patients with metastatic disease and <2 lymph nodes evaluated were excluded. Patients were divided into 2 groups: node positive and node negative.
MAIN OUTCOME MEASURES - The main outcome was nodal disease. The secondary outcome was overall survival.
RESULTS - A total of 42,257 patients with stage II/III rectal cancer underwent chemoradiation therapy and radical resection; 4170 (9.9%) patients had ypT0 tumors and 395 (9.5%) were node positive. Of patients with clinically node-negative disease (ie, pretreatment imaging), 6.2% were node positive after chemoradiation therapy and resection. In multivariable analysis, factors predictive of nodal disease included increasing (pretreatment) clinical N-stage, high tumor grade (3/4), perineural invasion, and lymphovascular invasion. Higher clinical T-stage was inversely associated with residual nodal disease. Overall 5-year survival was significantly different between patients with ypN0, ypN1, and ypN2 disease (87.4%, 82.2%, and 62.5%, p = 0.002).
LIMITATIONS - This study was limited by the lack of clinical detail in the database and the inability to assess recurrence.
CONCLUSIONS - Ten percent of patients with ypT0 tumors had positive nodes after chemoradiation therapy and resection. Factors associated with residual nodal disease included clinical nodal disease at diagnosis and poor histologic features. Patients with any of these features should consider radical resection regardless of tumor response. Others could be suitable for "watchful waiting" strategies. See Video Abstract at http://links.lww.com/DCR/A458.
Background - The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC.
Patients and methods - Patients were randomly received 60-66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1-5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05.
Results - A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%-28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55-1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009).
Conclusion - EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC.
Trial registration ID - NCT01494558.
© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
BACKGROUND - Planning and delivery of IMRT for locally advanced head and neck cancer (LAHNC) can be performed using sequential boost or simultaneous integrated boost (SIB). Whether these techniques differ in treatment-related outcomes including survival and acute and late toxicities remain largely unexplored.
METHODS - We performed a single institutional retrospective matched cohort analysis on patients with LAHNC treated with definitive chemoradiotherapy to 69.3 Gy in 33 fractions. Treatment was delivered via sequential boost (n = 68) or SIB (n = 141). Contours, plan evaluation, and toxicity assessment were performed by a single experienced physician. Toxicities were graded weekly during treatment and at 3-month follow up intervals. Recurrence-free survival, disease-free survival, and overall survival were estimated via Kaplan-Meier statistical method.
RESULTS - At 4 years, the estimated overall survival was 69.3% in the sequential boost cohort and 76.8% in the SIB cohort (p = 0.13). Disease-free survival was 63 and 69% respectively (p = 0.27). There were no significant differences in local, regional or distant recurrence-free survival. There were no significant differences in weight loss (p = 0.291), gastrostomy tube placement (p = 0.494), or duration of gastrostomy tube dependence (p = 0.465). Rates of acute grade 3 or 4 dysphagia (82% vs 55%) and dermatitis (78% vs 58%) were significantly higher in the SIB group (p < 0.001 and p = 0.012 respectively). Moreover, a greater percentage of the SIB cohort did not receive the prescribed dose due to acute toxicity (7% versus 0, p = 0.028).
CONCLUSIONS - There were no differences in disease related outcomes between the two treatment delivery approaches. A higher rate of grade 3 and 4 radiation dermatitis and dysphagia were observed in the SIB group, however this did not translate into differences in late toxicity. Additional investigation is necessary to further evaluate the acute toxicity differences.
BACKGROUND AND PURPOSE - This single institution phase I trial determined the maximum tolerated dose (MTD) of concurrent vorinostat and capecitabine with radiation in non-metastatic pancreatic cancer.
MATERIAL AND METHODS - Twenty-one patients received escalating doses of vorinostat (100-400mg daily) during radiation. Capecitabine was given 1000mg q12 on the days of radiation. Radiation consisted of 30Gy in 10 fractions. Vorinostat dose escalation followed the standard 3+3 design. No dose escalation beyond 400mg vorinostat was planned. Diffusion-weighted (DW)-MRI pre- and post-treatment was used to evaluate in vivo tumor cellularity.
RESULTS - The MTD of vorinostat was 400mg. Dose limiting toxicities occurred in one patient each at dose levels 100mg, 300mg, and 400mg: 2 gastrointestinal toxicities and one thrombocytopenia. The most common adverse events were lymphopenia (76%) and nausea (14%). The apparent diffusion coefficient (ADC) increased in most tumors. Nineteen (90%) patients had stable disease, and two (10%) had progressive disease at time of surgery. Eleven patients underwent surgical exploration with four R0 resections and one R1 resection. Median overall survival was 1.1years (95% confidence interval 0.78-1.35).
CONCLUSIONS - The combination of vorinostat 400mg daily M-F and capecitabine 1000mg q12 M-F with radiation (30Gy in 10 fractions) was well tolerated with encouraging median overall survival.
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
OPINION STATEMENT - Despite decades of high-quality research, the treatment of rectal cancer remains a work in progress. The interplay between chemotherapy, radiotherapy, and surgery is under constant rearrangement and refinement. Through this all, the desire to preserve the anal sphincters and quality of life remains at the forefront. In the past decade, standard of care for stage II or III rectal cancers in the USA has been neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection of the rectum. While timing and sequence of the CRT continues to evolve, surgical resection has remained essential in treatment. This stands in contrast to anal cancer, where surgery is reserved purely for salvage. This article describes a treatment strategy that attempts to treat rectal adenocarcinoma with CRT alone, reserving surgery for failure or salvage. Of the studies performed to date, a number are methodologically sound and show promise. However, the body of evidence has yet to reach a size to sway practitioners from the established trinity of chemotherapy, radiotherapy, and surgery. Interestingly, few trials administer post treatment full-dose systemic chemotherapy, which is the standard of care in patients undergoing surgical resection. Better identification of patients that will have complete cure from this approach, combined with long-term outcome data on salvage patients, is necessary for this therapy to be universally embraced.
BACKGROUND - Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC.
STUDY DESIGN - Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated.
RESULTS - There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT.
CONCLUSIONS - This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.
Copyright © 2016. Published by Elsevier Inc.
ABBREVIATIONS - EORTC/NCIC, European Organisation for Research and Treatment of Cancer/National Cancer Institute of CanadaGBM, glioblastomaOS, overall survivalPFS, progression-free survivalSEER, Surveillance, Epidemiology, and End ResultsTMZ, temozolomide.
OBJECT - This pilot study evaluated the utility of 3'-deoxy-3'[18F]-fluorothymidine ([(18)F]-FLT) positron emission tomography (PET) to predict response to neoadjuvant therapy that included cetuximab in patients with wild-type KRAS rectal cancers.
METHODS - Baseline [(18)F]-FLT PET was collected prior to treatment initiation. Follow-up [(18)F]-FLT was collected after three weekly infusions of cetuximab, and following a combined regimen of cetuximab, 5-FU, and radiation. Imaging-matched biopsies were collected with each PET study.
RESULTS - Diminished [(18)F]-FLT PET was observed in 3/4 of patients following cetuximab treatment alone and in all patients following combination therapy. Reduced [(18)F]-FLT PET following combination therapy predicted disease-free status at surgery. Overall, [(18)F]-FLT PET agreed with Ki67 immunoreactivity from biopsy samples and surgically resected tissue, and was predictive of treatment-induced rise in p27 levels.
CONCLUSION - These results suggest that [(18)F]-FLT PET is a promising imaging biomarker to predict response to neoadjuvant therapy that included EGFR blockade with cetuximab in patients with rectal cancer.
OBJECTIVE - We describe development and preliminary testing of Vanderbilt Head and Neck Symptom Survey-Recurrent/Metastatic (VHNSS-RM) to assess residual symptoms, tumor-related symptoms, and side effects from therapy.
METHODS - Items were identified through patient and provider interviews. Card sort selected high-yield and high-impact items. The VHNSS-RM was administered to 50 patients with recurrent/metastatic head and neck cancer (RMHNC).
RESULTS - The VHNSS-RM includes 12 unique symptoms (diet change, tongue movement affecting speech/swallowing, face/neck swelling, neck/jaw cramping, bad breath, drooling, wound drainage/pain/odor, nasal congestion/drainage, eyes watering, face/tongue/ear/scalp numbness, headaches, and confusion) and 7 unique psychosocial issues (burden to family/friends, lost independence, fear, embarrassment, mood swings, stress, and boredom).
CONCLUSIONS - The VHNSS-RM contains 35 physical and 12 psychosocial issues. The VHNSS-RM is feasible and not overly burdensome. Nineteen unique items may improve palliation to patients with RMHNC.
© The Author(s) 2015.