Supporting Life Adjustment in Patients With Lung Cancer Through a Comprehensive Care Program: Protocol for a Controlled Before-and-After Trial.

BACKGROUND: Lung cancer diagnosis affects an individual's quality of life as well as physical and emotional functioning. Information on survivorship care tends to be introduced at the end of treatment, but early intervention may affect posttreatment adjustment. However, to the best of our knowledge, no study has explored the effect of early information intervention on the return to work, family, and societal roles of lung cancer survivors. OBJECTIVE: We report the study protocol of a comprehensive care prehabilitation intervention designed to facilitate lung cancer survivors' psychological adjustment after treatment. METHODS: A comprehensive care program was developed based on a literature review and a qualitative study of patients with lung cancer and health professionals. The Lung Cancer Comprehensive Care Program consists of educational videos and follow-up visits by a family medicine physician. To prevent contamination, the control group received routine education, whereas the intervention group received routine care and intervention. Both groups completed questionnaires before surgery (T0) and at 1-month (T1), 6-month (T2), and 1-year (T3) follow-up visits after surgery. The primary outcome was survivors' psychological adjustment to cancer 6 months after pulmonary resection. RESULTS: The historical control group (n=441) was recruited from September 8, 2021, to April 20, 2022, and the intervention group (n=350) was recruited from April 22, 2022, to October 17, 2022. All statistical analyses will be performed upon completion of the study. CONCLUSIONS: This study examined the effectiveness of an intervention that provided general and tailored informational support to lung cancer survivors, ranging from before to the end of treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05078918; https://clinicaltrials.gov/ct2/show/NCT05078918. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54707.

Unmet Supportive Care Needs after Non-Small Cell Lung Cancer Resection at a Tertiary Hospital in Seoul, South Korea.

The aim of this study is to identify the prevalence and predictors of unmet needs of non-small cell lung cancer (NSCLC) patients undergoing surgical resection in Seoul, South Korea. A total of 949 patients who completed survey questionnaires that included the Cancer Survivors' Unmet Needs Korean version (CaSUN-K), fear of cancer recurrence (FCR) inventory-short form, and European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) were recruited from January to October 2020. Multivariable logistic regression was used to determine the potential correlation of significant unmet needs, defined as any moderate or strong need, for each domain of CaSUN-K. Of the 949 participants, the mean age was 63.4 ± 8.8 years old, and 529 (55.7%) were male. Overall, 91.8% of participants reported one or more unmet need. The highest domains of moderate-to-strong unmet needs were existential survivorship (59.1%), comprehensive cancer care (51.2%), and information (49.7%). High FCR and poor emotional function were associated with moderate-to-strong unmet needs across all domains of CaSUN-K. NSCLC survivors with a recent diagnosis had more frequent disease-related unmet needs. Interventions to reduce the unmet needs of NSCLC patients should focus on relieving FCR and improving emotional functioning. Furthermore, emphasis should be placed on decreasing disease-related needs, particularly for early survivors of lung cancer during the re-entry phase.

The efficacy of adjuvant chemotherapy with capecitabine and cisplatin after surgery in locally advanced esophageal squamous cell carcinoma: a multicenter randomized phase III trial.

There is limited evidence for the effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC). This study aimed to assess whether adjuvant capecitabine and cisplatin improve survival compared to surgery alone among patients with locally advanced ESCC. This is a multicenter randomized controlled trial. Patients were eligible if they underwent curative resection for ESCC staged T2-4 or N1 and M0 according to the TNM cancer staging system sixth edition. The intervention group received four cycles of adjuvant chemotherapy (capecitabine: 1,000 mg/m 2 b.i.d for 14 days, and intravenous cisplatin: 75 mg/m2 at day 1, every 3 weeks). A total of 136 patients were randomly assigned to either the adjuvant chemotherapy group (n = 68) or surgery-alone group (n = 68). Seven patients who rejected chemotherapy after randomization were excluded from the final analysis. The cumulative incidence of recurrence within 18 months after surgery was significantly lower in the adjuvant chemotherapy group than in the surgery-alone group (hazard ratio [HR]: 0.49; 95% confidence interval (CI): 0.25-0.95]. However, the 5- and 10-year disease-free survival did not differ between treatment groups (HR: 0.84; 95% CI: 0.53-1.34 and HR: 0.76; 95% CI: 0.50-1.18, respectively). Adjuvant chemotherapy after curative resection in patients with locally advanced ESCC reduced early recurrence but had no statistically significant increase in the long-term disease-free survival. Due to the limited sample size of this study, additional randomized controlled trials with larger sample sizes are necessary.

Treatment outcomes in patients with extranodal marginal zone B-cell lymphoma of the lung.

OBJECTIVES: To evaluate clinical presentations, treatment modalities, and outcomes of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma by stage strata. METHODS: We retrospectively reviewed 51 patients diagnosed with pulmonary MALT lymphoma between January 2003 and December 2015. To compare treatment modalities and outcomes, we stratified the patients into low-stage (IE/IIE) and high-stage (IIIE/IVE) groups using modified Ann Arbor staging. Progression-free survival was estimated using Kaplan-Meier curves, and differences were compared using the log-rank test. A hazard ratio of progression by stage strata, adjusted for other clinical variables, was determined using a Cox adjusted proportional hazards model. RESULTS: The majority of patients had stage IE disease (76.5%; 39 of 51). With advancing stage, patients were more likely to have respiratory and B symptoms and higher International Prognostic Index scores. The most common treatment modality was surgical resection in low-stage patients (33 of 43) and chemotherapy in high-stage patients (7 of 8). At a median follow-up of 40.7 months, progression-free survival was longer for low-stage patients (median, 40.7 months vs 24.9 months; P < .001), and high-stage patients were 9.2 times more likely to progress (hazard ratio, 9.24; 95% confidence interval, 1.93-44.36). Among 30 patients with surgically resected stage IE disease, 8 with central lesions were treated via lobectomy and 22 with peripheral lesions were treated via lobectomy (n = 8) or limited resection (n = 14). One of these patients, with a central lesion, experienced disease recurrence. CONCLUSIONS: Our findings suggest that the clinical course of low-stage pulmonary MALT lymphoma, for which the mainstay of treatment is surgical resection, might be indolent.

A Randomized Phase II Study of Leucovorin/5-Fluorouracil with or without Oxaliplatin (LV5FU2 vs. FOLFOX) for Curatively-Resected, Node-Positive Esophageal Squamous Cell Carcinoma.

PURPOSE: The optimal perioperative treatment for resectable esophageal squamous cell carcinoma (ESCC) remains controversial. We evaluated the efficacy and safety of leucovorin and 5-fluorouracil (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX) combination chemotherapies administered adjuvantly for curatively-resected, node-positive ESCC. MATERIALS AND METHODS: Patients with pathologically node-positive esophageal cancer after curative R0 resection were enrolled and randomly assigned to receive LV5FU2 or FOLFOX biweekly for up to eight cycles. The primary endpoint was disease-free survival (DFS). RESULTS: Between 2011 and 2015, 62 patients were randomized into the two treatment groups (32 in the LV5FU2 arm and 30 in the FOLFOX arm). The median age was 60 years and both groups had similar pathologic characteristics in tumor, nodal status, and location. Treatment completion rates were similarly high in both groups. The DFS rate at 12 months was 67% in the LV5FU2 group and 63% in the FOLFOX group with a hazard ratio of 1.3 (95% confidence interval [CI], 0.66 to 2.62). After a median follow-up period of 27 months, the median DFS was 29.6 months (95% CI, 4.9 to 54.2) in the LV5FU2 arm and 16.8 months (95% CI, 7.5 to 26.1) in the FOLFOX arm (p=0.428), respectively, while the median overall survival was not reached in either arm. Grade 3 or 4 neutropenia was more frequent in patients in the FOLFOX arm than the LV5FU2 arm (20.0% vs. 3.1%). CONCLUSION: The addition of oxaliplatin (FOLFOX) did not lead to better efficacy compared to LV5FU2 chemotherapy in an adjuvant setting in node-positive ESCC patients.

Epigenetic inactivation of heparan sulfate (glucosamine) 3-O-sulfotransferase 2 in lung cancer and its role in tumorigenesis.

BACKGROUND: This study was aimed at investigating the functional significance of heparan sulfate (glucosamine) 3-O-sulfotransferase 2 (HS3ST2) hypermethylation in non-small cell lung cancer (NSCLC). METHODOLOGY/ PRINCIPAL FINDINGS: HS3ST2 hypermethylation was characterized in six lung cancer cell lines, and its clinical significance was analyzed using 298 formalin-fixed paraffin-embedded tissues and 26 fresh-frozen tissues from 324 NSCLC patients. MS-HRM (methylation-specific high-resolution melting) and EpiTYPER(TM) assays showed substantial hypermethylation of CpG island at the promoter region of HS3ST2 in six lung cancer cell lines. The silenced gene was demethylated and re-expressed by treatment with 5-aza-2'-deoxycytidine (5-Aza-dC). A promoter assay also showed the core promoter activity of HS3ST2 was regulated by methylation. Exogenous expression of HS3ST2 in lung cancer cells H460 and H23 inhibited cell migration, invasion, cell proliferation and whereas knockdown of HS3ST2 in NHBE cells induced cell migration, invasion, and cell proliferation in vitro. A negative correlation was observed between mRNA and methylation levels of HS3ST2 in 26 fresh-frozen tumors tissues (ρ = -0.51, P = 0.009; Spearman's rank correlation). HS3ST2 hypermethylation was found in 95 (32%) of 298 primary NSCLCs. Patients with HS3ST2 hypermethylation in 193 node-negative stage I-II NSCLCs with a median follow-up period of 5.8 years had poor overall survival (hazard ratio = 2.12, 95% confidence interval = 1.25-3.58, P = 0.005) compared to those without HS3ST2 hypermethylation, after adjusting for age, sex, tumor size, adjuvant therapy, recurrence, and differentiation. CONCLUSIONS/ SIGNIFICANCE: The present study suggests that HS3ST2 hypermethylation may be an independent prognostic indicator for overall survival in node-negative stage I-II NSCLC.

EGFR mutation testing in patients with advanced non-small cell lung cancer: a comprehensive evaluation of real-world practice in an East Asian tertiary hospital.

INTRODUCTION: Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea. METHODS: Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records. RESULTS: This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (P<0.001). The median time elapsed between cancer diagnoses and receiving EGFR testing results was 21 days. EGFR testing was most frequently ordered by oncologists (57.7%), pulmonologists (31.9%), and thoracic surgeons (6.6%). EGFR testing was more commonly requested for women, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7%) were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma. CONCLUSIONS: In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive cases warrants the need for generalized testing in Asian NSCLC patients.

Web-based tailored education program for disease-free cancer survivors with cancer-related fatigue: a randomized controlled trial.

PURPOSE: To determine whether an Internet-based tailored education program is effective for disease-free cancer survivors with cancer-related fatigue (CRF). PATIENTS AND METHODS: We randomly assigned patients who had completed primary cancer treatment within the past 24 months in any of four Korean hospitals and had reported moderate to severe fatigue for at least 1 week to participate in a 12-week, Internet-based, individually tailored CRF education program or to receive routine care. We based the program on the CRF guidelines of the National Comprehensive Cancer Network (NCCN) and incorporated the transtheoretic model (TTM). At baseline and 12 weeks, we used the Brief Fatigue Inventory (BFI) and Fatigue Severity Scale (FSS) as primary outcomes and the Hospital Anxiety and Depression Scale (HADS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) for secondary outcomes. RESULTS: We recruited 273 participants and randomly assigned 136 to the intervention group. Compared with the control group, the intervention group had an improvement in fatigue as shown by a significantly greater decrease in BFI global score (-0.66 points; 95% CI -1.04 to -0.27) and FSS total score (-0.49; 95% CI, -0.78 to -0.21). In secondary outcomes, the intervention group experienced a significantly greater decrease in HADS anxiety score (-0.90; 95% CI, -1.51 to -0.29) as well as global quality of life (5.22; 95% CI, 0.93 to 9.50) and several functioning scores of the EORTC QLQ-C30. CONCLUSION: An Internet-based education program based on NCCN guidelines and TTM may help patients manage CRF.

Treatment outcomes for HIV-uninfected patients with multidrug-resistant and extensively drug-resistant tuberculosis.

BACKGROUND: Multidrug-resistant (MDR) tuberculosis (TB) is more difficult to treat than is drug-susceptible TB. To elucidate the optimal therapy for MDR TB, we assessed the treatment outcomes and prognostic factors for patients with MDR TB. METHODS: This study included patients who received an individualized treatment regimen for MDR TB at Samsung Medical Center, a tertiary referral hospital in Seoul, Korea, from January 1995 through December 2004. To identify the prognostic factors related to favorable treatment outcomes, univariate comparison and multiple logistic regression were performed. RESULTS: Of 155 patients, 18 (12%) had newly diagnosed MDR TB, 81 (52%) had previously received treatment with first-line drugs, and 56 (36%) had received treatment with second-line drugs. The isolated strains were resistant to a median of 5 drugs. Twenty-seven patients (17%) had extensively drug-resistant (XDR) TB at the start of treatment. Outcome assessment revealed that 102 patients (66%) were cured or completed therapy. The treatment success rates did not differ significantly between patients with non-XDR MDR TB and those with XDR TB (66% vs. 67%). Surgical resection was performed more frequently for patients with XDR TB than for those with non-XDR MDR TB (48% vs. 17%). Combined surgical resection, body mass index >/=18.5 (calculated as the weight in kilograms divided by the square of the height in meters), use of >4 effective drugs, and a negative sputum smear result were independent predictors of a favorable outcome. CONCLUSIONS: Early aggressive treatment comprising at least 4 effective drugs and surgical resection, when indicated, may improve the outcome for patients with MDR TB or XDR TB.

Adjuvant chemotherapy with 5-fluorouracil and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma.

BACKGROUND: In this study we explored the effectiveness of adjuvant chemotherapy in node-positive, resected thoracic esophageal squamous cell carcinoma patients. METHODS: A prospective study of postoperative chemotherapy in N1 esophageal cancer patients who received curative resection was conducted and compared with the historical control group in regard to recurrence rate, patterns of failure, disease-free survival rate, and overall survival rate. The postoperative chemotherapy consisted of cisplatin (60 mg/m2 intravenously) and 5-fluorouracil (1,000 mg/m2 per day) in a continuous infusion for 4 days. Three cycles were administered at 3-week intervals. RESULTS: Forty patients were accrued from January 1998 to January 2003 at Samsung Medical Center for adjuvant chemotherapy. The historical control group consisted of 52 patients who received curative resection but not adjuvant chemotherapy during the same period of time. The 3-year disease-free survival rate was 47.6% in the adjuvant group and 35.6% in the control group (p = 0.049). The estimated 5-year overall survival rates were 50.7% in the adjuvant group and 43.7% in the control group (p = 0.228). The significant predictive factors for tumor recurrence were the number of positive lymph nodes (p = 0.008) and the adjuvant chemotherapy (p = 0.030). CONCLUSIONS: This study suggests that the postoperative chemotherapy may prolong disease-free survival in lymph node-positive, curatively resected esophageal cancer patients. The postoperative treatment modality for esophageal cancer patients should be determined according to the lymph node status and a randomized phase III clinical trial is warranted using adjuvant chemotherapy if the esophageal cancer is lymph node-positive.