Background
Induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LA‐SCCHN) often compromises compliance with subsequent chemoradiotherapy (CRT), which ...negatively affects outcomes. Here, we assessed the combination of paclitaxel (PTX), carboplatin (CBDCA), and cetuximab (Cmab) as IC for unresectable LA‐SCCHN.
Methods
Induction chemotherapy consisted of weekly CBDCA area under the plasma concentration‐time curve = 1.5, PTX 80 mg/m2 and Cmab with an initial dose of 400 mg/m2 followed by 250 mg/m2 for 8 weeks. Following IC, CDDP (20 mg/m2, 4 days × 3 cycles) and concurrent radiotherapy (70 Gy/35 fr) were started. Primary endpoint was the proportion of CRT completion (%CRT completion). PCE was planned to be deemed effective if the Bayesian posterior probability (PP), defined as the probability that %CRT completion was larger than the threshold value of 65%, exceeded 84%.
Results
Thirty‐five patients were enrolled. Cases were hypopharynx/oropharynx/larynx in 17/17/1 patients, all at Stage IV. Of 35 patients, 34 (97%) completed IC and 32 received CRT and met the criteria of full analysis set (FAS). In FAS, the %CRT completion was 96.9%, and PP was 99.9%, exceeding the prespecified boundary of 84%. Mean cumulative dose and relative to dose intensity of CDDP in CRT was 232.5 mg/m2 and 100%, respectively. Response rate was 88.6% by IC and 93.8% in the CRT phase. Three year overall survival was 83.5%. Main grade 3 toxicities included neutropenia (11.4%) and skin rash (5.7%) during IC; and oral mucositis (31.3%) and neutropenia (12.5%) during CRT. No grade 4 toxicity or treatment‐related death was seen.
Conclusions
PCE as IC was feasible, with promising efficacy and no effect on compliance with subsequent CRT in unresectable LA‐SCCHN.
The combination of PCE as induction chemotherapy was feasible and had no effect on compliance with subsequent chemoradiotherapy (CRT) with CDDP, and provided encouraging efficacy in high‐risk unresectable locally advanced squamous cell carcinoma of the head and neck (LA‐SCCHN). The regimen is a favorable alternative to TPF for LA‐SCCHN patients who required more aggressive treatment, herein sequential CRT.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and study aims:
The novel method of image-enhanced endoscopy (IEE) named blue laser imaging (BLI) can enhance the contrast of surface vessels using lasers for light illumination. BLI has ...two IEE modes: high contrast mode (BLI-contrast) for use with magnification, and bright mode (BLI-bright), which achieves a brighter image than BLI-contrast and yet maintains the enhanced visualization of vascular contrast that is expected for the detection of tumors from a far field of view. The aim of this study is to clarify the effect of BLI-bright with a far field of view compared to BLI-contrast and commonly available narrow-band imaging (NBI).
Patients and methods:
Patients with neoplasia, including early cancer in the pharynx, esophagus, stomach, or colorectum, were recruited and underwent tandem endoscopy with BLI and NBI systems. Six sets of images of the lesions were captured with a changing observable distance from 3 to 40 mm. Individual sets of images taken from various observable distances were assessed for visibility among BLI-bright, BLI-contrast, and NBI modes. The brightness and contrast of these images were also analyzed quantitatively.
Results:
Of 51 patients, 39 were assessed. Image analysis indicated that only BLI-bright maintained adequate brightness and contrast up to 40 mm and had significantly longer observable distances compared to the other methods. Furthermore, BLI-bright enhanced the visualization of serious lesions infiltrating into deeper layers, such as esophageal lamina propria or gastric submucosal cancers.
Conclusions:
BLI-bright will be a helpful tool for the far-field view with IEE in organs with wider internal spaces such as the stomach.
This study was performed to evaluate the concordance in pathological assessments of blood and lymphatic vessel invasion (BLI) in pT1 colorectal cancers and to assess the effect of diagnostic ...criterion on consistency in the assessment of BLI.
Forty consecutive patients undergoing surgical resection of pT1 colorectal cancers were entered into this study. H&E-stained, D2-40-stained and elastica-stained slides from the tumours were examined by 18 pathologists from seven countries. The 40 cases were divided into two cohorts with 20 cases each. In cohort 1, pathologists diagnosed BLI using criteria familiar to them; all Japanese pathologists used a criterion of BLI from the Japanese Society for Cancer of the Colon and Rectum (JSCCR). In cohort 2, all pathologists used the JSCCR diagnostic criterion.
In cohort 1, diagnostic concordance was moderate in the US/Canadian and European pathologists. There were no differences in the consistency compared with results for Japanese pathologists, and no improvement in the diagnostic concordance was found for using the JSCCR criterion. However, in cohort 2, the JSCCR criterion decreased the consistency of BLI diagnosis in the US/Canadian and European pathologists. The level of decreased consistency in the assessment of BLI was different between the US/Canadian and European pathologists.
A uniform criterion strongly influences the diagnostic consistency of BLI but may not always improve the concordance. Further study is required to achieve an objective diagnosis of BLI in colorectal cancer. The varying effects of diagnostic criterion on the pathologists from Japan, the USA/Canada and Europe might reflect varied interpretations of the criterion. Internationally accepted criterion should be developed by participants from around the world.
Hydrazine‐embedded unsubstituted butterfly‐shaped biphenothiazine and its sulfoxides were synthesized by dimerization of 1,9‐dibromophenothiazine, which was prepared by realizing selective ...debromination at the 3,7‐positions of 1,3,7,9‐tetrabromophenothiazine. cis/trans‐Biphenothiazine sulfoxide was selectively prepared by changing the oxidation temperature to control the inversion rate of the butterfly shape of the intermediate. Their butterfly‐shapes, conformations, photophysical properties (UV‐vis absorption, fluorescence), and redox properties were elucidated by X‐ray analysis, DFT calculations, spectral and electrochemical measurements. Fluorescent hydrazine‐embedded biphenothiazine sulfoxides and bicarbazoles were applied to cell imaging of HeLa cells. The bicarbazoles exhibited high fluorescence signals in the cells with low toxicity.
Traffic lights: Hydrazine‐embedded butterfly‐shaped biphenothiazine sulfoxides were synthesized and their physicochemical properties such as fluorescence were elucidated. Fluorescent hydrazine‐embedded heterocyclic compounds, butterfly‐shaped biphenothiazine sulfoxides, helix‐ and bowl‐shaped bicarbazoles, were applied to fluorescence cell imaging.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Transient CD4
T cell depletion led to the proliferation of tumor-specific CD8
T cells in the draining lymph node and increased infiltration of PD-1
CD8
T cells into the tumor, which resulted in ...strong anti-tumor effects in tumor-bearing mice. This is a first-in-human study of IT1208, a defucosylated humanized anti-CD4 monoclonal antibody, engineered to exert potent antibody-dependent cellular cytotoxicity.
Patients with advanced solid tumors were treated with intravenous IT1208 at doses of 0.1 or 1.0 mg/kg. The first patient in each cohort received a single administration, and the other patients received two administrations of IT1208 on days 1 and 8.
Eleven patients were enrolled in the 0.1 mg/kg (n = 4) and 1.0 mg/kg cohorts (n = 7). Grade 1 or 2 infusion-related reactions was observed in all patients. Decreased CD4
T cells in peripheral blood due to IT1208 were observed in all patients and especially in those receiving two administrations of 1.0 mg/kg. CD8
T cells increased on day 29 compared with baseline in most patients, resulting in remarkably decreased CD4/8 ratios. One microsatellite-stable colon cancer patient achieved durable partial response showing increased infiltration of both CD4
and CD8
T cells into tumors after IT1208 administration. Moreover, transcriptomic profiling of the liver metastasis of the patient revealed upregulation of the expression of interferon-stimulated genes, T cell activation-related genes, and antigen presentation-related genes after IT1208 administration. Two additional patients with gastric or esophageal cancer achieved stable disease lasting at least 3 months.
IT1208 monotherapy successfully depleted CD4
T cells with a manageable safety profile and encouraging preliminary efficacy signals, which warrants further investigations, especially in combination with immune checkpoint inhibitors.
Aggressive adult T‐cell leukemia/lymphoma (ATL) has an extremely poor prognosis and is hyperendemic in Okinawa, Japan. This study evaluated two prognostic indices (PIs) for aggressive ATL, the ATL‐PI ...and Japan Clinical Oncology Group (JCOG)‐PI, in a cohort from Okinawa. The PIs were originally developed using two different Japanese cohorts that included few patients from Okinawa. The endpoint was overall survival (OS). Multivariable Cox regression analyses in the cohort of 433 patients revealed that all seven factors for calculating each PI were statistically significant prognostic predictors. Three‐year OS rates for ATL‐PI were 35.9% (low‐risk, n = 66), 10.4% (intermediate‐risk, n = 256), and 1.6% (high‐risk, n = 111), and those for JCOG‐PI were 22.4% (moderate‐risk, n = 176) and 5.3% (high‐risk, n = 257). The JCOG‐PI moderate‐risk group included both the ATL‐PI low‐ and intermediate‐risk groups. ATL‐PI more clearly identified the low‐risk patient subgroup than JCOG‐PI. To evaluate the external validity of the two PIs, we also assessed prognostic discriminability among 159 patients who loosely met the eligibility criteria of a previous clinical trial. Three‐year OS rates for ATL‐PI were 34.5% (low‐risk, n = 42), 9.2% (intermediate‐risk, n = 109), and 12.5% (high‐risk, n = 8). Those for JCOG‐PI were 22.4% (moderate‐risk, n = 95) and 7.6% (high‐risk, n = 64). The low‐risk ATL‐PI group had a better prognosis than the JCOG‐PI moderate‐risk group, suggesting that ATL‐PI would be more useful than JCOG‐PI for establishing and examining novel treatment strategies for ATL patients with a better prognosis. In addition, strongyloidiasis, previously suggested to be associated with ATL‐related deaths in Okinawa, was not a prognostic factor in this study.
ATL‐PI with its three strata more clearly identified low‐risk patients than the dichotomous JCOG‐PI. The results of this study suggest that ATL‐PI will be more useful than JCOG‐PI for establishing and examining novel treatment strategies in clinical research settings.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Exclusion of patients with a history of other cancer treatment except in situ situation has been considered to be inevitable for clinical trials investigating survival outcome. However, there have ...been few reports confirming these influences on surgical outcome of lung cancer patients ever.
Multi-institutional, individual data from patients with non–small cell lung cancer resected between 2000 and 2013 were collected. The patients were divided into two groups: those with a history of gastrointestinal tract cancer (GI group) and those without any history (non-GI group). We compared the outcomes with well-matched groups using propensity scoring to minimize bias related to the nonrandomness. The influence of gastrointestinal tract cancer stage, disease-free interval, and treatment method for gastrointestinal tract cancer on the surgical outcome of non–small cell lung cancer was examined.
We analyzed 196 patients in the GI group and 3732 in the non-GI group. In unmatched cohort, multivariate analyses showed that a history of gastrointestinal tract cancer did not affect overall survival or recurrence-free survival. Independent predictors of poor prognosis included older age, male sex, high carcinoembryonic antigen levels and advanced clinical stage of non–small cell lung cancer. The two groups in the matched cohort demonstrated equivalent overall survival and recurrence-free survival, even in patients with clinical stage I. Gastrointestinal tract cancer stage, disease-free interval and treatment method for gastrointestinal tract cancer were not associated with outcomes.
History of early gastrointestinal tract cancer completely resected is not always necessary for exclusion criteria in clinical trial of lung cancer.
Background and Aim
Surgical resection is the standard local therapy for patients with colorectal liver metastases (CRLM). However, elderly and vulnerable patients sometimes have various organ ...dysfunctions. We have to conduct nonsurgical local therapies for those patients who might not tolerate surgery or systemic chemotherapy.
Methods
We retrospectively reviewed medical records of 254 patients who underwent local therapies, including surgery, radiofrequency ablation (RFA), and stereotactic body radiation therapy (SBRT), for CRLM from January 2010 to December 2016, at seven tertiary‐care institutions in Japan. This study was designed to include elderly, vulnerable patients who received local therapy for CRLM. For those undergoing liver resection, only those having one or more points of the Charlson comorbidity index (CCI) were enrolled.
Results
Of the total 169 enrolled patients, 122 patients underwent surgery, 42 RFA, and 5 SBRT as the first local therapy for CRLM. Median overall survival from the first local therapy was 5.9 years for the surgery group, 2.7 years for the RFA group, and 3.8 years for the SBRT group. The proportion of the patients with CCI ≧3 was significantly higher in the group of RFA/SBRT than surgery (P < 0.0001). In selected patients with CCI ≧3, there was no difference of the median survival time between the surgery group and the RFA group.
Conclusions
We could have other treatment options to provide nonsurgical local therapies (RFA/SBRT) for elderly, vulnerable CRLM patients who have risks for surgery.
The number of elderly patients with colorectal liver metastasis (CRLM) is increasing. This article indicates the possibility of other treatment options to provide nonsurgical local therapies (radiofrequency ablation/stereotactic body radiation therapy) for elderly, vulnerable CRLM patients who have risks for surgery.
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