Safety and efficacy of concurrent carboplatin or cetuximab plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin

Background : Locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is usually treated with cisplatin (CDDP)-based chemoradiotherapy, except when patients are elderly or have renal, cardiac, or neurogenic dysfunction. This study compared the safety and efficacy of concurrent carboplatin (CBDCA) to cetuximab (Cmab) plus radiotherapy (RT) in patients ineligible for CDDP treatment. Methods : We retrospectively analyzed LASCCHN patients who received CBDCA plus RT (n = 29) or Cmab plus RT (n = 18) due to ineligibility for CDDP treatment at two Japanese institutions between August 2006 and December 2015. Results : Patients characteristics for CBDCA plus RT and Cmab plus RT were: median age, 74 and 75 years; 0-1 performance status, 90% and 100%; main primary tumor site, hypopharynx 52% (n = 15) and oropharynx 39% (n = 7); and stage IV, 90% (n = 26) and 50% (n = 9), respectively. With a median follow-up time of 60.0 months for CBDCA plus RT and 53.6 months for Cmab plus RT, 3-year locoregional control rates were 56% versus 58%, and median progression-free survival was 42.7 versus 11.6 months. CBDCA plus RT was associated with more grade 3/4 hematologic toxicities, including neutropenia and thrombocytopenia, whereas Cmab plus RT was associated with more grade 3/4 oral mucositis and radiation dermatitis. Conclusions : CBDCA or Cmab as a concurrent systemic therapy with RT is a possible treatment option for LASCCHN patients ineligible for CDDP treatment, although attention to hematological toxicity should be paid

An autopsy case report of adult-onset Krabbe disease : Comparison with an infantile-onset case

Krabbe disease is a lysosomal storage disease caused by a deficiency of the galactocerebrosidase (GALC) enzyme, which leads to demyelination of the central and peripheral nervous systems. Almost all patients with Krabbe disease are infants, and this is the first report of adult-onset cases that describe pathological findings. Here, we present two autopsy cases: a 73-year-old female and a 2-year-old male. The adult-onset case developed symptoms in her late thirties and was diagnosed by the identification of GALC D528N and L634S mutations and by T2-weighted magnetic resonance imaging; she had increased signal in the white matter along the pyramidal tract to the bilateral precentral gyrus, as well as from the triangular part to the posterior horn of the lateral ventricle. Microscopically, Kluver-Barrera staining was pale in the white matter of the precentral gyrus and occipito-thalamic radiation, and a few globoid cells were observed. The GALC mutations that were identified in the present adult-onset case do not completely inactivate GALC enzyme activity, resulting in focal demyelination of the brain

Biomarker analysis for patients with pancreatic cancer treated with nanoliposomal irinotecan plus 5-fluorouracil/leucovorin

Abstract Background Nanoliposomal irinotecan plus fluorouracil/leucovorin (5-FU/LV) is a standard second-line therapy for patients with pancreatic cancer. Identification of biomarkers is important to determine appropriate treatment strategies. We investigated the clinical practice outcomes and biomarkers associated with the nanoliposomal irinotecan plus 5-FU/LV regimen. Methods We retrospectively reviewed the data of patients treated with nanoliposomal irinotecan plus 5-FU/LV as a second or subsequent treatment after gemcitabine-based therapy between June 2020 and March 2021 at Shizuoka Cancer Center. Results We analyzed 55 consecutive patients who met the selection criteria. At a median of 9.4 months, median progression-free survival (PFS) and median overall survival (OS) were 2.3 and 6.6 months, respectively. Multivariate analysis showed that Glasgow prognostic score (GPS) was significantly associated with PFS (hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.09–4.30; P = 0.028) and OS (0 vs. 1 or 2: HR 2.46; 95% CI 1.15–5.25; P = 0.029). The OS was significantly longer in patients with CA19–9 response than in those without CA19–9 response (12.6 vs. 5.6 months; HR 0.24; 95% CI 0.08–0.75; P = 0.014). Conclusions Nanoliposomal irinotecan was efficacious and tolerable in clinical practice. GPS and CA19–9 response were good candidates as predictive biomarkers, whereas GPS was a good candidate prognostic biomarker for the nanoliposomal irinotecan plus 5-FU/LV regimen

An autopsy case report of adult-onset Krabbe disease : Comparison with an infantile-onset case

Krabbe disease is a lysosomal storage disease caused by a deficiency of the galactocerebrosidase (GALC) enzyme, which leads to demyelination of the central and peripheral nervous systems. Almost all patients with Krabbe disease are infants, and this is the first report of adult-onset cases that describe pathological findings. Here, we present two autopsy cases: a 73-year-old female and a 2-year-old male. The adult-onset case developed symptoms in her late thirties and was diagnosed by the identification of GALC D528N and L634S mutations and by T2-weighted magnetic resonance imaging; she had increased signal in the white matter along the pyramidal tract to the bilateral precentral gyrus, as well as from the triangular part to the posterior horn of the lateral ventricle. Microscopically, Kluver-Barrera staining was pale in the white matter of the precentral gyrus and occipito-thalamic radiation, and a few globoid cells were observed. The GALC mutations that were identified in the present adult-onset case do not completely inactivate GALC enzyme activity, resulting in focal demyelination of the brain

Risk factors for esophageal fistula in thoracic esophageal squamous cell carcinoma invading adjacent organs treated with definitive chemoradiotherapy: a monocentric case-control study

Abstract Background Standard treatment for unresectable esophageal squamous cell carcinoma (ESCC) without distant metastasis is definitive chemoradiotherapy (dCRT), in which the incidence of esophageal fistula (EF) is reported to be 10–12%. An ad hoc analysis of JCOG0303, a phase II/III trial of dCRT for patients with unresectable ESCC (including non-T4b), suggested that esophageal stenosis is a risk factor for EF. However, risk factors for EF in patients limited to T4b ESCC treated with dCRT have yet to be clarified. The aim of this study was to investigate risk factors for EF in T4b thoracic ESCC treated with dCRT. Methods We retrospectively analyzed the data of consecutive T4b thoracic ESCC patients who were treated with dCRT (cisplatin and fluorouracil) at Shizuoka Cancer Center between April 2004 and September 2015. Results Excluding 8 patients with esophageal fistula clearly attributable to other iatrogenic interventions, the data of 116 patients who met the inclusion criteria were analyzed. Esophageal fistula was observed in 28 patients (24%). Although the fistula was closed in 5 patients, overall survival was significantly shorter in patients who experienced esophageal fistula (8.0 vs. 26.8 months; p < 0.0001). Among four potential variables extracted in univariate analysis, namely, total circumferential lesion, elevated CRP level, elevated white blood cell count, and anemia, the first two were revealed as risk factors for esophageal fistula in multivariate analysis. Conclusions This study demonstrated that total circumferential lesion and CRP ≥1.00 mg/dL are risk factors for esophageal fistula in T4b thoracic ESCC treated with dCRT. Trial registration This study was retrospectively registered

Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer

SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m(2)) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort (N = 19; unselected population, including three patients with MET-amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m2. Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose dependent. Grade a. 3 AEs were observed in 39.5% of patients and considered drug related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m2 in the dose-expansion cohort, comprising patients with MET-amplified tumors (N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m2 has acceptable tolerability and modest antitumor activity in patients with MET-amplified gastric cancer