Hironaga Satake

Long-term outcome of transoral organ-preserving pharyngeal endoscopic resection for superficial pharyngeal cancer.

BACKGROUND Early detection of pharyngeal cancer has been difficult. We reported that narrow-band imaging (NBI) endoscopy can detect superficial pharyngeal cancer, and these lesions can be treated endoscopically. OBJECTIVE To assess the safety and long-term efficacy of transoral organ-preserving pharyngeal endoscopic resection (TOPER) for superficial pharyngeal cancer. DESIGN AND SETTING Retrospective 2-center cohort study. PATIENTS The study included 104 consecutive patients with superficial pharyngeal cancer. INTERVENTION TOPER with the patients under general anesthesia. MAIN OUTCOME MEASUREMENTS Safety of the procedure, long-term survival, clinical outcome. RESULTS A total of 148 consecutive lesions were resected in 104 patients. There was no severe adverse event. Temporary tracheostomy was required in 17 patients (16%) to prevent airway obstruction. The median fasting period and hospital stay after TOPER were 2 days (range 1-20 days) and 8 days (range 3-58 days), respectively. Ninety-six patients (92%) had no local recurrence or distant metastases. Local recurrence at the primary site developed in 6 patients, but all were resolved by repeat TOPER. With a median follow-up period of 43 months (range 3-96 months), the overall survival rate at 5 years was 71% (95% CI, 59-82). Cause-specific survival rate at 5 years was 97% (95% CI, 93-100). The cumulative development rate of multiple cancers in pharyngeal mucosal sites at 5 years was 22% (95% CI, 12-33). The pharynx was preserved in all patients, and they experienced no loss of function. LIMITATION Retrospective design. CONCLUSIONS Peroral endoscopic resection of superficial pharyngeal cancer is a feasible and effective treatment with curative intent.

Clinical outcome after endoscopic resection for superficial pharyngeal squamous cell carcinoma invading the subepithelial layer.

BACKGROUND AND STUDY AIMS The curability of endoscopic resection for superficial pharyngeal squamous cell carcinoma (SPSCC) has not been fully elucidated, particularly for lesions invading the subepithelial layer, which carry the risk of metastasis. The aim of this study was to evaluate the curative potential of endoscopic resection for SPSCC invading the subepithelial layer. PATIENTS AND METHODS From June 2002 to July 2010, 198 SPSCCs in 176 consecutive patients were treated by endoscopic resection at two tertiary referral centers. Selection criteria were initial endoscopic resection, histologically proven squamous cell carcinoma invading the subepithelial layer, no lymph node or distant metastasis before endoscopic resection, and no prior treatment for pharyngeal squamous cell carcinoma. Endoscopic resection was performed under general anesthesia. Long-term survival and clinical outcomes were retrospectively evaluated. RESULTS Among 176 consecutive patients, 50 lesions in 47 patients (all male; median age 64 years) were histologically diagnosed from endoscopic resection specimens as having subepithelial invasion. Median tumor thickness was 1000 μm (range 200 - 10 000 μm). Six patients developed local recurrence (13 %; 95 % confidence interval [CI] 3.1 % - 22.4 %), and all were cured with organ-preserving intervention. After a median follow-up period of 71 months (range 27 - 116 months), one patient (2 %; 95 %CI 0 - 6.3 %) developed neck lymph node metastasis. A total of 14 patients (30 %) were followed for 5 years or more, and 5-year overall survival and disease-specific survival rates were 84.5 % (95 %CI 73 % - 96 %) and 100 %, respectively. CONCLUSIONS Endoscopic resection has curative potential as a minimally invasive treatment option for SPSCC that invades the subepithelial layer.

Radial incision and cutting method for refractory stricture after nonsurgical treatment of esophageal cancer.

Strictures remaining after nonsurgical treatment for esophageal cancer are generally more refractory to endoscopic balloon dilation (EBD) when compared with anastomotic strictures. The aim of the present study was to evaluate the efficacy and safety of a radial incision and cutting (RIC) method for the treatment of refractory strictures after nonsurgical treatment of esophageal cancer. All subjects complained of grade 2 or worse dysphagia, even after at least 10 sessions of EBD. Between August 2009 and May 2012, eight consecutive patients with refractory esophageal stricture after nonsurgical treatments, including chemoradiotherapy (CRT) alone (n = 3), CRT followed by salvage endoscopic treatment (n = 3), or endoscopic submucosal dissection (ESD; n = 2), underwent the RIC procedure. After the RIC procedure, dysphagia in all the patients dramatically improved to grade 1 or 0 without any major complications; however, the long-term efficacy was unfavorable as only 37.5 % (3 /8) demonstrated adequate lumen patency at 3 months, and re-intervention was necessary in six patients (75 %).

Treatment Strategy for Superficial Pharyngeal Squamous Cell Carcinoma Synchronously Combined with Esophageal Cancer

Background: Esophageal squamous cell carcinoma (ESCC) is often synchronously accompanied by pharyngeal squamous cell carcinoma (PSCC). However, treatment strategies for these synchronous cancers have not been established. Aim: To evaluate retrospectively the effects of both chemoradiotherapy (CRT) targeted for invasive ESCC on synchronous superficial PSCC and additional endoscopic resection (ER) for PSCC. Patients and Methods: Screening endoscopy in the pharynx was performed in newly diagnosed ESCC patients. CRT combined with 5-fluorouracil (5-FU) and cisplatin (CDDP) was administered to all patients. The effect on superficial PSCC was only evaluated for 5-FU-CDDP chemotherapy that excluded the pharynx from the radiation field. When PSCC was remnant or recurrent in patients evaluated at complete response (CR) of ESCC, ER was performed on the PSCC. Results: Fourteen cases of superficial PSCC (4.0%) were detected in 348 ESCC patients. Three PSCC reached CR in 8 ESCC-CR patients, while all 3 lesions recurred. No treatment response was found in the remaining 11 PSCC. As a second treatment, ER for 8 PSCC was completed in the 8 ESCC-CR patients, with one complication due to pneumonia. Conclusions: Standard 5-FU-CDDP CRT targeted for invasive ESCC did not demonstrate a sufficient efficacy for superficial PSCC, while ER even for PSCC after chemotherapy was curative.

A phase II trial of 1st-line modified-FOLFOXIRI plus bevacizumab treatment for metastatic colorectal cancer harboring RAS mutation: JACCRO CC-11

FOLFOXIRI plus bevacizumab is considered a standard initial therapy for metastatic colorectal cancer (mCRC). However, few prospective trials have evaluated triplet therapy plus bevacizumab in patients with RAS mutant mCRC. Patients with an age of 20 to 75 years, and unresectable, measurable tumors harboring RAS mutation were given first-line treatment with bevacizumab (5 mg/kg on day 1) plus modified-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, levofolinate 200 mg/m2, and fluorouracil 2400 mg/m2 as a 46-h continuous infusion on day 1, repeated every 2 weeks). The primary endpoint was the objective response rate (ORR) as evaluated by an external review board. Progression-free survival (PFS), overall survival, early tumor shrinkage (ETS), depth of response (DpR), and safety were secondary endpoints. Among 64 patients who were enrolled between October 2014 and August 2016, 62 were evaluable for efficacy (right-sided tumors in 27%). ORR and disease control rate were 75.8% (95% confidence interval [CI] 65.1-86.5) and 96.8%, respectively. ETS was 73.8%, and median DpR was 49.2%. Median PFS was 11.5 (95% CI 9.5-14.0) months as of the cut-off date of September 2017. Adverse events of grade 3 or 4 were neutropenia (54%), hypertension (32%), diarrhea (13%), anorexia (11%), peripheral neuropathy (2%), and febrile neutropenia (5%). In conclusion, this prospective trial demonstrated for the first time that FOLFOXIRI plus bevacizumab is an active first-line treatment for patients with RAS mutant mCRC. Modified-FOLFOXIRI plus bevacizumab might become an alternative regimen of triplet chemotherapy for mCRC in Japan.

Early Clinical Outcomes of Anal Squamous Cell Carcinoma Treated with Concurrent Chemoradiotherapy with 5-Fluorouracil Plus Mitomycin C in Japanese Patients: Experience at a Single Institution

Concurrent chemoradiotherapy with 5-fluorouracil plus mitomycin C has been established as a standard therapy for non-metastatic anal squamous cell carcinoma in the West. However, there have been few reports of chemoradiotherapy for anal squamous cell carcinoma in Japan. We retrospectively investigated seven consecutive anal squamous cell carcinoma patients who were treated with concurrent chemoradiotherapy consisting of 5-fluorouracil plus mitomycin C with a total irradiation of 59.4 Gy. The patients consisted of two males and five females. Clinical stages II/IIIA/IIIB accounted for four, one and two patients, respectively. Full-dose irradiation was completed in all patients. Median relative dose intensities of 5-fluorouracil and mitomycin C were both 99%. All patients achieved complete response. At a median follow-up of 37.5 months, one patient experienced local recurrence. The most common grade 3/4 acute toxicities were dermatitis in 100% and anal pain in 71%. There was no treatment-related death. Concurrent chemoradiotherapy appears to be tolerable and effective in Japanese patients with anal squamous cell carcinoma.

Neutrophil-to-lymphocyte ratio as a predictive or prognostic factor for gastric cancer treated with nivolumab: a multicenter retrospective study

Introduction The neutrophil-to-lymphocyte ratio (NLR) is effective as a predictive factor for lung cancer treated with nivolumab. The objective of this study was to determine the effectiveness of NLR for patients with advanced gastric cancer (AGC) treated with nivolumab. Methods This was a multicenter, retrospective study of patients with AGC treated with nivolumab from June 2017 to December 2017. The NLRs were calculated before the first cycle (NLRpre) and two weeks after the first administration (NLRpost). Results Twenty-six patients were enrolled (males 19, females 7) with a median age of 64 years. The overall response rate was 15%. The median PFS was 80 days (range, 11 – 265) and the median OS was 290 days (range, 21 – 332). Stratified with high NLR (≥5) and low NLR (<5), the median PFS was shorter in the high NLRpre arm (87 vs. 45 days; p=0.066) and significantly shorter in the high NLRpost arm (94 vs. 28 days; p=0.014). The median OS was significantly shorter in the high NLRpre arm (290 vs. 175 days; p=0.008) and in the high NLRpost arm (290 vs. 69 days; p<0.001). Conclusion NLR may be an effective prognostic factor in patients with AGC treated with nivolumab.

Role of Predictive Value of the Modified Glasgow Prognostic Score for Later-line Chemotherapy in Patients With Metastatic Colorectal Cancer

Micro‐Abstract The survival and safety of patients with metastatic colorectal cancer treated with trifluridine/tipiracil or regorafenib as later‐line chemotherapy were retrospectively examined according to the modified Glasgow Prognostic Score (mGPS). Overall and progression‐free survival were strongly correlated with mGPS in all patients. The frequency of adverse events was generally similar in each mGPS group. Background Assessment of patient factors is essential for selecting later‐line chemotherapy in patients with metastatic colorectal cancer (mCRC). The efficacy, prognosis, and safety of each treatment regimen according to nutritional and inflammatory status still remain to be elucidated. Patients and Methods A total of 550 patients with mCRC who were registered in the REGOTAS study (Regorafenib versus TAS‐102 as Salvage‐line in patients with colorectal cancer refractory to standard chemotherapies: a multicenter observational study, UMIN 000020416) and treated with trifluridine/tipiracil (TFTD) or regorafenib as a later‐line therapy were retrospectively stratified according to the modified Glasgow Prognostic Score (mGPS), which divided patients into mGPS 0 to 2 by serum albumin and C‐reactive protein, and compared. Results The median overall survival (OS) of patients with mGPS 0, 1, and 2 was 10.0 months (95% confidence interval [CI], 9.2‐11.6 months), 6.5 months (95% CI, 5.3‐7.1 months), and 3.9 months (95% CI, 3.3‐4.9 months), respectively. The median progression‐free survival (PFS) with mGPS 0, 1, and 2 was 2.5 months (95% CI, 2.1‐3.0 months), 2.0 months (95% CI, 1.9‐2.3 months), and 1.7 months (95% CI, 1.4‐1.9 months), respectively. There were significant differences by mGPS in both OS and PFS (all P < .001). No significant differences in OS and PFS were observed between the patient groups treated with TFTD and regorafenib in each mGPS group. In patients aged ≥ 65 years with mGPS 2, the OS and PFS were worse with regorafenib than with TFTD (OS: hazard ratio, 1.45; 95% CI, 0.93‐2.25; P = .097; PFS: hazard ratio, 1.57, 95% CI, 1.01‐2.44; P = .047), but there were no consistent trends observed as mGPS increased. The frequency of grade 3 and more adverse events was generally similar in each mGPS group. The multivariate analyses showed that mGPS was the strongest predictive factor for OS. Conclusions The mGPS before later‐line chemotherapy is strongly correlated with survival in patients with mCRC.

Hyperprogressive Disease in the Irradiation Field after a Single Dose of Nivolumab for Gastric Cancer: A Case Report

Following the ATTRACTION-2 study, nivolumab was approved for advanced gastric cancer in Japan. However, pseudoprogression and hyperprogressive disease have been reported in patients treated with immune checkpoint inhibitors. We report a patient with gastric cancer who received nivolumab after radiotherapy only to experience rapid progression within the irradiation field after the first immunotherapy session. A 66-year-old man with dysphagia visited our hospital and was diagnosed with stage IV gastroesophageal cancer (human epidermal growth factor receptor-2 score = 0). He commenced a G-SOX regimen (S-1 80 mg/m2 on days 1–14 and oxaliplatin 100 mg/m2 on day 1, repeated every 3 weeks) in June 2017. The dysphagia worsened despite 3 cycles of G-SOX, and computed tomography (CT) revealed constriction of the gastroesophageal junction. To ameliorate the dysphagia, palliative chemoradiotherapy (S-1 and 50.4 Gy in 28 fractions) was performed starting in August 2017. The patient’s dysphagia had not resolved after completing radiotherapy, and pain on swallowing worsened. Nivolumab (3 mg/m2 every 2 weeks) was administered 7 days after the completion of radiotherapy. The patient experienced malaise and worsening dysphagia before the second cycle. CT 15 days after the first nivolumab administration revealed rapid progression in the irradiation field. His general condition rapidly deteriorated, and he died 24 days after the first administration. This episode suggests that administration of nivolumab after radiotherapy may be a risk factor for hyperprogressive disease.

A prospective Phase II study to examine the relationship between quality of life and adverse events of first-line chemotherapy plus cetuximab in patients with KRAS wild-type unresectable metastatic colorectal cancer: QUACK trial

A prospective trial has not been performed to investigate associations between quality of life (QOL), adverse events (AEs), and overall survival (OS) in the first‐line treatment with cetuximab plus standard chemotherapy for advanced/metastatic colorectal cancer (mCRC). Associations between patient outcome and health‐related QOL (HRQOL) together with skin toxicity‐related QOL were prospectively evaluated using EORTC QLQ‐C30 and DLQI questionnaires. One hundred and forty mCRC patients were analyzed in this study, and 87.8% received pre‐emptive skin treatment. Skin toxicity had no clinical impact on HRQOL or skin‐related QOL during the first 8 weeks and throughout the study period. An early skin reaction with a grade ≥2 at 8 weeks was significantly associated with a favorable OS compared with a grade of ≤1 (HR, 0.50; 95% CI, 0.24‐0.95; P = .035) and was confirmed to be an independent predictor of OS (HR, 0.48; 95% CI, 0.21‐0.97; P = .040). Patients symptomatic at baseline who responded to treatment had improved HRQOL compared to nonresponding patients. Severe mucositis/stomatitis had a statistically significant and clinically meaningful negative impact on HRQOL (mean changes from baseline throughout the study period in global health status were −12.64 for a grade of ≥2 vs −0.35 for a grade of 0 or 1 (P = .005)). In conclusion, severe early skin reactions predict favorable OS for patients treated with cetuximab plus chemotherapy without impairing QOL. In addition, mucositis/stomatitis was the most substantial AE compromising both QOL and treatment compliance.