Katsuhiro Omae

Efficacy of prophylactic cranial irradiation in patients with limited-disease small-cell lung cancer who were confirmed to have no brain metastasis via magnetic resonance imaging after initial chemoradiotherapy

Background Prophylactic cranial irradiation (PCI) is recommended for patients with limited-disease small-cell lung cancer (LD-SCLC) who achieved good response to definitive chemoradiotherapy. However, most clinical studies lacked brain imaging scans before PCI. Our study aimed to investigate whether PCI has a survival benefit in patients who have no brain metastases (BM) confirmed via magnetic resonance imaging (MRI) before PCI. Results Eighty patients were included in this study. Sixty patients received PCI (PCI group) and 20 patients did not (non-PCI group). OS was not significantly different between the two groups. The median OS time was 4.3 years (95% CI: 2.6 years–8.6 years) in the PCI group and was not reached (NR) (95% CI: 1.9 years–NR) in the non-PCI group (p = 0.542). Moreover, no differences were observed in the 3-year rates of PFS (46.2% and 44.4%, p = 0.720) and cumulative incidence of BM (24.0% vs. 27%, p = 0.404). Conclusions Our result suggests that PCI may not have a survival benefit in patients with LD-SCLC confirmed to have no BM after initial therapy, even if patients achieve a good response to definitive chemoradiotherapy. Patients and Methods We retrospectively evaluated patients with LD-SCLC who were confirmed to have no BM via MRI after initial chemoradiotherapy at the Shizuoka Cancer Center between September 2002 and August 2015. The overall survival (OS), progression-free survival (PFS), and cumulative incidence of BM were estimated using the Kaplan–Meier method between patients who received PCI and those who did not. Propensity score matching was used to balance baseline characteristics.

Impact of Cancer Cachexia on Hospitalization-associated Physical Inactivity in Elderly Patients with Advanced Non-small-cell Lung Cancer

Objective: New or worsening disability can develop in elderly patients in just 1 week of hospitalization for acute illness. Elderly patients with cancer, particularly those with cancer cachexia, are vulnerable to disability. This study aimed to explore the impact of hospitalization and cachexia on physical activity (PA) in elderly patients during chemotherapy. Methods: We prospectively enrolled 18 patients aged ≥70 years with newly-diagnosed, advanced non-small-cell lung cancer scheduled to initiate first-line chemotherapy. PA was measured using an accelerometer (Lifecorder®, Suzuken Co., Ltd., Japan). Mean daily steps at baseline, during hospitalization, and subsequent weeks (1st, 2nd, and 3rd week after discharge) were compared. Results: A total of 30 hospitalizations for chemotherapy were evaluated in 18 patients with a median age of 74.5 years. The median number of baseline daily steps was 3756. Fifteen cases (50%) showed fewer daily steps during hospitalization and no recovery to baseline level during the 1st week after discharge. Long hospitalizations (≥8 days) and the presence of cachexia were associated with persistent physical inactivity. One patient developed disability within 30 days after hospitalization. Conclusions: Physical inactivity was frequently seen after hospitalization for chemotherapy in elderly patients with advanced lung cancer. Longer in-hospital days and the presence of cancer cachexia caused slow recovery from physical inactivity. Individualized hospitalization planning based on careful consideration of patient age and the presence of cancer cachexia may be needed to prevent physical inactivity and disability.

Clinical Factors Predicting Detection of T790M Mutation in Rebiopsy for EGFR-Mutant Non–small-cell Lung Cancer

Micro‐Abstract A higher T790M detection rate is desirable for introducing third‐generation epidermal growth factor receptor‐tyrosine kinase inhibitor treatment. This study evaluated the clinical factors influencing the incidence of T790M. Postsurgery recurrence and longer total duration of epidermal growth factor receptor‐tyrosine kinase inhibitor treatment before rebiopsy correlated with high incidence of T790M mutation. Therefore, rebiopsy after disease progression is aggressively encouraged in patients with these factors. Background: T790M, a secondary epidermal growth factor receptor (EGFR) mutation, accounts for approximately 50% of acquired resistance to EGFR‐tyrosine kinase inhibitors (TKIs). To facilitate the use of third‐generation EGFR‐TKIs to potentially overcome T790M‐mediated resistance, we evaluated the clinical factors influencing the incidence of T790M mutation. Patients and Methods: We retrospectively screened patients with non–small‐cell lung cancer harboring EGFR mutations with progressive disease who were rebiopsied between January 2013 and December 2016. Factors influencing T790M status were evaluated by univariate and multivariate analysis. Results: Among 131 rebiopsied patients for whom EGFR mutation status was available, 58 (44%) had T790M mutations. Patient characteristics at rebiopsy were not significantly different between T790M‐positive and ‐negative groups, except for surgical history (postsurgery recurrence). Total duration of EGFR‐TKI treatment before rebiopsy, TKI‐free interval, EGFR‐TKI treatment history immediately before rebiopsy, continuation of initial EGFR‐TKI beyond progressive disease, progression‐free survival after initial TKI treatment, and rebiopsy site (other than fluid samples) significantly influenced T790M status. The incidence of T790M mutation was shown by multivariate analysis to be significantly higher in patients with postsurgery recurrence and total duration of EGFR‐TKI treatment ≥ 1 year before rebiopsy (odds ratio, 4.2; 95% confidence interval, 1.3‐15.7 and odds ratio, 4.4; 95% confidence interval, 1.1‐19.8, respectively). Conclusion: Postsurgery recurrence and longer total duration of EGFR‐TKI treatment before rebiopsy may represent useful predictive markers for T790M detection. In patients with these clinical factors, rebiopsies are more recommended to detect T790M mutation.

CYFRA 21-1 predicts the efficacy of nivolumab in patients with advanced lung adenocarcinoma:

CYFRA 21-1 is a prognostic marker for non–small cell lung cancer. The serum CYFRA 21-1 level is also known as an adjunct for the diagnosis of lung squamous cell carcinoma. This study aimed to examine whether CYFRA 21-1 has predictive implications for nivolumab therapy in patients with advanced lung adenocarcinoma. Of the 79 patients who were treated with nivolumab therapy at the Shizuoka Cancer Center between December 2015 and September 2016, we retrospectively reviewed the data of 50 patients. The patient characteristics were as follows: age <70/≥70 years: 43 (86%)/7; male/female: 31 (62.0%)/19; Eastern Cooperative Oncology Group performance status 0–1/2: 43 (86%)/7; smoking status: no/yes: 18 (36%)/32; epidermal growth factor receptor mutation status negative/positive: 36 (72%)/14; CYFRA 21-1 ≥2.2/<2.2 ng/mL: 28 (56%)/22; carcinoembryonic antigen ≥5/<5 ng/mL: 29 (58%)/21; and number of prior regimens 2–3/≥4: 16 (32%)/34. With a median follow-up of 263.5 (range, 64–352) days, the median progression-free survival was 70 days. The clinical variables investigated using univariate analysis were as follows: age (p = 0.423), carcinoembryonic antigen (p = 0.888), epidermal growth factor receptor mutation status (p = 0.105), performance status (p = 0.968), sex (p = 0.210), number of prior regimens (p = 0.146), CYFRA 21-1 (p = 0.026), and smoking status (p = 0.041). A multivariate analysis identified a serum CYFRA 21-1 level ≥2.2 ng/mL as an independent predictor of a favorable outcome (hazard ratio, 0.44; 95% confidence interval, 0.23–0.85; p = 0.015; median progression-free survival, 155 vs 51.5 days). In conclusion, CYFRA 21-1 might be an independent predictor of outcome for patients with advanced lung adenocarcinoma treated with nivolumab.

Risk factors for local recurrence after lobectomy and lymph node dissection in patients with non-small cell lung cancer: Implications for adjuvant therapy

OBJECTIVES The objective of this study was to investigate clinicopathological risk factors for local recurrence in patients who underwent either complete resection with lobectomy or more extensive resection with hilar and mediastinal lymph node dissection for non-small cell lung cancer (NSCLC). The role of adjuvant therapy was also explored. MATERIALS AND METHODS We reviewed the records of 1012 consecutive stage I-III NSCLC patients who underwent complete resection. The median follow-up time was 59 months. The risk factors for local recurrence were investigated by multivariate analysis using Coxs proportional hazards regression model. RESULTS Local recurrence was identified in 9.4% of the patients. The most significant risk factor for local recurrence was lymph node metastasis (N1: hazard ratio [HR]=2.27, p=0.009; N2: HR=6.85, p<0.0001). For the subgroup of patients with lymph node metastasis (n=289), the independent risk factors for local recurrence were N2 disease with N1 metastasis (N2 with N1; HR=3.46, p<0.0001) and non-receipt of adjuvant platinum-based chemotherapy (HR=1.91, p=0.018). The 5-year freedom from local recurrence rates were 96.1%, 84.1%, 85.0%, and 53.5% for N0, N1, skip N2, and N2 with N1 stages (p<0.0001). CONCLUSION Local recurrence is significantly associated with poor overall survival. Therefore, local control is essential for radical cure of NSCLC. N2 with N1 status was the primary risk factor for local recurrence, while adjuvant chemotherapy improved local control. These data have important implications for postoperative radiotherapy and highlight the need to devise more effective eligibility criteria for this modality in patients with lymph node metastasis.

ILD-NSCLC-GAP index scoring and staging system for patients with non-small cell lung cancer and interstitial lung disease

BACKGROUND AND OBJECTIVE Patients with advanced non-small cell lung cancer (NSCLC) and interstitial lung disease (ILD) are commonly excluded from most clinical trials because of acute exacerbation (AE) of ILD triggered by chemotherapy. Data on the efficacy and feasibility of chemotherapy are limited in this patient population. Recently, the ILD-GAP index and staging system was reported as a clinical prognostic factor associated with mortality in patients with ILD. Therefore, we evaluated the incidence of ILD-AE during the surveillance term in this study and the prognosis in patients with NSCLC and ILD using a modified ILD-GAP (ILD-NSCLC-GAP) index scoring system. MATERIALS AND METHODS The medical records of patients with NSCLC and ILD who underwent a pulmonary function test before initiation of platinum-based chemotherapy as first-line treatment at the Shizuoka Cancer Center between September 2002 and December 2014 were reviewed retrospectively. Among these patients, we compared the incidence of ILD-AE, one-year survival rate, and overall survival (OS) between the ILD-NSCLC-GAP index scores and stages. RESULTS Of the 78 patients included, 21 (27%; 95% confidence interval [CI], 18%-38%) had ILD-AE during the surveillance term in this study. The one-year survival and median OS rates were 49% and 11.3 months, respectively. The incidence of ILD-AE increased gradually and the one-year survival and median OS rates decreased gradually with increasing ILD-NSCLC-GAP index scores and stages. CONCLUSION The ILD-NSCLC-GAP index scoring and staging system may be a useful tool to calculate a prediction of the incidence of ILD-AE and its prognosis for patients with NSCLC and ILD.

Depth of invasion in superficial oral tongue carcinoma quantified using intraoral ultrasonography: Intraoral US for Tongue Carcinoma

Depth of invasion (DOI) in oral carcinoma has been integrated into the primary tumor categories in the current tumor‐node‐metastasis staging (8th edition). However, there is no standard modality to determine DOI preoperatively. The aims of the present study were to evaluate the accuracy of a preoperative measurement of DOI using ultrasonography (US) for superficial oral tongue carcinomas, and to correlate the values obtained with histologically determined DOI measurements.

Safety profile of prophylactic rescue dosing of immediate-release oral opioids in cancer patients

BackgroundAppropriate prophylactic rescue dosing of opioids is considered effective for cancer pain relief, but no study has reported the safety of such prophylactic rescue. We compared the safety of prophylactic rescue dosing of immediate-release oral opioids with that of regular rescue dosing.MethodsThe study included 103 cancer patients who used either immediate-release morphine syrup or immediate-release oxycodone powder at Shizuoka Cancer Center between January and December 2016. Patients were divided into those who mostly used (prophylactic group) and those who never used (regular group) prophylactic rescue doses of opioids and compared the incidence of adverse events (AEs). We also investigated whether the prophylactic rescue dose negatively interfered with its objective activity, such as meals.ResultsIncidence of each AE in the prophylactic versus regular groups was as follows: somnolence, 20.6% versus 14.3%; nausea, 22.1% versus 17.1%; constipation, 19.1% versus 20.0%; urinary retention, 1.5% versus 2.9%; delirium, 4.4% versus 8.6%; and pruritus, 0% versus 2.9%. No serious AE associated with prophylactic rescue dosing was observed. No significant difference was observed in the incidence of any AE between the two groups (p > 0.05, Fisher’s exact test). No AE interfered with the objective activity of the prophylactic rescue dose.ConclusionIncidence of AEs associated with prophylactic rescue dosing is not different from that associated with regular rescue dosing. In addition, the prophylactic rescue dose did not adversely affect its objective activity, suggesting the safety of appropriate prophylactic rescue dosing was similar to that of regular rescue dosing.Trial registrationThe study approval number in the institution; H29-J30–29–1-3. Registered June 5, 2017.

Impact of Interstitial Lung Disease Classification on the Development of Acute Exacerbation of Interstitial Lung Disease and Prognosis in Patients with Stage III Non-Small-Cell Lung Cancer and Interstitial Lung Disease Treated With Chemoradiotherapy

Introduction: Data on the efficacy and risk of curative-intent chemoradiotherapy in patients with inoperable stage III non-small-cell lung cancer (NSCLC) and interstitial lung disease (ILD) are limited. The aim of this study was to explore the impact of ILD classification on acute exacerbation (AE) of ILD and prognosis in patients with stage III NSCLC and ILD treated with chemoradiotherapy. Materials and methods: We retrospectively reviewed the medical records of patients with stage III NSCLC and ILD treated with curative-intent chemoradiotherapy as the first-line treatment at the Shizuoka Cancer Center between June 2009 and May 2014. Results: Of 37 patients, 17 (46%) developed AE of ILD worse than grade 3 within 1 year after the last irradiation. In univariate analysis, the incidence rate of AE of ILD was lower in patients with a non-usual interstitial pneumonia (UIP) pattern than in those with a UIP pattern. Multivariate analysis showed that ILD classification was significantly associated with the incidence of AE of ILD. The median overall survival (OS) durations in patients with a non-UIP pattern and a UIP pattern were 16.5 and 9.3 months, respectively. In univariate analysis, patients with a non-UIP pattern showed better survival. Multivariate analysis showed that ILD classification was a significant independent prognostic factor. Conclusion: The incidence of AE of ILD was high in patients with stage III NSCLC and ILD treated with chemoradiotherapy as the first-line treatment. However, diagnosis of a non-UIP pattern could predict lower risk of AE of ILD and longer OS durations.

Feasibility of early multimodal interventions for elderly patients with advanced pancreatic and non-small-cell lung cancer: Early multimodal intervention for elderly cancer patients

Combinations of exercise and nutritional interventions might improve the functional prognosis for cachectic cancer patients. However, high attrition and poor compliance with interventions limit their efficacy. We aimed to test the feasibility of the early induction of new multimodal interventions specific for elderly patients with advanced cancer Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) programme.