Background

Thymic neoplasms are rare in incidence and relatively slow growing with late presentation. Thymoma are considered as potentially malignant and thymic carcinoma are malignant. Because of rarity and under reporting in India, there is an unmet need for treatments and response in our population.

Methods

This is a retrospective analytical study of patients diagnosed with thymoma and thymic carcinoma from June 2014 to June 2017 from a regional cancer centre in India. Data were recorded for epidemiological, clinical, histopathological, staging and treatment and outcome from patient files after taking consent.

Results

A total of 24 total patients were diagnosed and taken for treatment at our institute. The incidence of thymoma and thymic carcinoma appears to be relatively similar (1.4:1). Most of the patients presented in Masaoka Stage III and IV constituting 50% and 42%, respectively. Predominant WHO histological types were B3 and C. Most of the patients received chemotherapy either in neoadjuvant setting or palliative setting. Stage III patients with unresectabe tumors received NACT followed by surgery and RT. Stage IV patients received chemotherapy. The regimens used were cisplatin, doxorubicin, cyclophosphamide (CAP) and cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC) in both the NACT and palliative setting. Stage III patients had 2 yr PFS and 2 yr OS of 75% and 82.5% with a median OS of 30 months. For the patients with stage IV most of the patients had a durable response, with 2 yr PFS and OS of 40% and 60%, respectively. Responses are more durable with ADOC than with other regimens.

Conclusions

Thymoma and thymic carcinoma are rare tumours with low incidence but these tumours are highly responsive to chemotherapy with considerable PFS and OS. Patients treated with the ADOC regimen responded well with durable response.

Legal entity responsible for the study

Kidawi Cancer Institute.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Sarcopenia, defined as decreased skeletal muscle mass, is prevalent and associated with poor prognosis in various solid tumors. This study aimed to determine the prognostic role of sarcopenia in patients with advanced gastric cancer (AGC).

Methods

This retrospective study consisted of 140 consecutive patients who underwent palliative chemotherapy for AGC. A cross-sectional area of muscle at the level of the third lumbar vertebra (L3) was measured using baseline computed tomography (CT) scans. Sarcopenia was defined as a L3 skeletal muscle index of ≤ 49 cm²/m² for men and ≤ 31 cm²/m² for women using Korean-specific cutoffs. We compared the overall survival (OS) and clinical characteristics of patients with and without sarcopenia.

Results

The median age was 67 years, and 133 (95%) patients had metastatic disease. Sarcopenia was present in 67 patients (47.9%) and was significantly related to male sex (p < 0.001) and low body mass index (p = 0.002). Patients with sarcopenia had a significantly shorter OS than those without sarcopenia (median, 6.8 months vs. 10.3 months, respectively; p = 0.033). In the multivariable analysis, sarcopenia was an independent prognostic factor of poor OS (hazard ratio, 1.51, p = 0.029); no response to chemotherapy (p < 0.001), no second-line chemotherapy (p < 0.001), metastatic sites ≥ 3 (p < 0.001), and low serum albumin level (p = 0.033) were also independent prognostic factors of poor OS.

Conclusions

Sarcopenia, as determined by baseline CT, can be used to predict poor prognosis in AGC patients treated with palliative chemotherapy.

Legal entity responsible for the study

Young Saing Kim.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

The combined therapy of nedaplatin and amrubicin showed promising effect for advanced non-small-cell lung cancer patients in our previous phase I/II study (Ogawara et al. Chemotherapy. 2014;60(3):180-4.). In the phase I study, nedaplatin 100 mg/m² and amrubicin 25 mg/m² was recommended. In the phase II study, 17 out of 35 patients achieved a partial response, and the ORR was 48.6%. In the study, nedaplatin and amrubicin tend to be effective especially for the patients with squamous cell lung cancer (Sq-LC). Therefore, we assessed the efficacy and safety of the combination chemotherapy for patients with untreated, advanced or relapsed Sq-LC.

Methods

We did a single-armed, open-label, phase II study at 6 institutions in Nagasaki, Japan. Eligibility criteria included pathologically proven squamous cell lung cancer with stage IIIB/IV or postoperative recurrence, age 20 to 75 years, Eastern Cooperative Oncology Group performance status of 0-1, adequate organ function. Primary endpoint was overall response rate (ORR) and the secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS). This trial was registered with the UMIN Clinical Trials Registry, number UMIN000007587, and is closed to new participants.

Results

Between November 2012 and March 2016, 21 patients were enrolled. The patients were administered nedaplatin (100 mg/m², day 1) plus amrubicin (25mg/m², day 1-3) every 4 weeks. ORR was 33.3%, disease control rate was 71.4%, median duration of PFS was 4.2 months, median duration of OS was 14.6 months. Adverse events of grade 3/4 were neutropenia (38.1%), thrombocytopenia (9.5%), anemia (9.5%), febrile neutropenia (9.5%).

Conclusions

Combination therapy of nedaplatin and amrubicin could be an effective and tolerable first-line treatment option for patients with advanced or relapsed Sq-LC.

Clinical trial identification

UMIN000007587.

Legal entity responsible for the study

Nagasaki University Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

In the 2016 Japanese Society guidelines for cancer of the colon and rectum, it is recommended to measure carcinoembryonic antigen (CEA) of the patient with colorectal cancer (CRC) after curative surgery every 1 to 3 months, as it is helpful to judge for recurrence of the disease. Although, it is reported that postoperative CEA level is more informative than preoperative CEA level for predicting prognosis (Tsuyoshi K, Yoshifumi S, Meier H et al. Association of Preoperative and Postoperative Serum Carcinoembryonic Antigen and Colon Cancer Outcome. JAMA Oncology. Publish online December 21, 2017), the association between persistently elevated CEA level after surgical resection and prognosis is still unclear. This study aimed to evaluate whether perioperative CEA level was useful for estimation of the prognosis in stage III CRC.

Methods

This retrospective study was conducted at the Cancer Institute Hospital of Japanese foundation of cancer research. A total of 505 consecutive patients who underwent curative resection for stage III CRC from March 2005 to December 2010 were identified. Postoperative CEA was measured within 12 weeks after surgery. High CEA level was defined as more than 5ng/ml. We examined disease-free survival (DFS), overall survival (OS) and the association of prognostic variables with DFS and OS.

Results

A total of 505 patients [272 (54%) male; median age 62 (23-85) years] were enrolled in this study. Patients with high CEA level of preoperatively and postoperatively were 5.5% (28/505) and 30% (153/505), respectively. The 3-year DFS rate for all patients was 74.5% and the 5-year OS rate for all patients was 87.5%. The 3-year DFS rate in patients with normal postoperative CEA level tended to be higher than in patients with high postoperative CEA level. Furthermore, the 5-year OS rate in patients with normal postoperative CEA level was significantly higher than in patients with high postoperative CEA level. In the multivariate analysis, N-stage, pathology and venous invasion were predictive factors of DFS. And pathology and postoperative CEA level were predictive factors of OS.

Conclusions

High postoperative CEA level may be a negative predictive factor for OS in patients who underwent curative resection for stage III CRC.

Legal entity responsible for the study

Ryotaro Kozuki.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Although the role of adjuvant chemotherapy of resected gastric cancer has been established, whether the delay of treatment impacts on clinical outcome has not been studied yet. The optimal time interval from surgery to adjuvant chemotherapy is also not known, either. We reported preliminary data previously in 2015. Herein, we added number of patients and updated their follow-up data for survival to empower statistical significance.

Methods

Patients who diagnosed of stage II-III gastric adenocarcinoma between 2009 and 2016 in Kyung Hee University hospital were included. We retrospectively collected patients’ data such as demographics, TNM stage, types of adjuvant chemotherapy, time interval (TI) between surgery and the first day of adjuvant chemotherapy. Patients were dichotomized based on TI which was predetermined as 3, 4, 5, 6, 7, or 8 weeks. Median disease-free survival (DFS) and overall survival (OS) were analyzed according to TI. In addition, in this updated analysis, we investigated whether the planned adjuvant chemotherapy was completed, and the reason of delay if TI was more than 4 weeks.

Results

One hundred and seventy two patients were identified. Median follow-up duration was 40.8 (3-109) months. Median TI was 4.1 (2.1-9.8) weeks. As expected, TNM stage (II vs III) had significant effect on DFS (Not reached [NR] vs 4.3 years, p = 0.001) and OS (NR vs 7 years, p = 0.008). DFS of patients with TI < 4 weeks (n = 66, 38.4%) was significantly superior compared to those with TI ≥ 4 weeks (n = 106, 61.6%) (8.1 vs 6.0 years, Hazard ratio [HR] 1.803, 95% Confidence Interval [CI]: 1.067-3.045, p = 0.025). OS was also significantly differented according to TI of 4 weeks favoring TI < 4 weeks (NR vs 7.0 years, HR 2.149, 95% CI: 1.173-3.939, p = 0.011). Other predetermined TI was not associated with survival outcomes. After adjusting the effect of stage by multivariate analysis, TI < 4 weeks had still favorable impact on DFS (HR 1.737, 95% CI: 1.026-2.939, p = 0.040) as well as OS (HR 2.076, 95% CI: 1.132-3.807, p = 0.018).

Conclusions

This study suggests that adjuvant chemotherapy for gastric cancer can be initiated within 4 weeks after surgery. Delay more than 4 weeks from any reasons could be harmful in terms of patients’ survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Cytological examination of urine is the most widely used noninvasive pathologic screen for bladder urothelial carcinoma (BLCA); however, inadequate diagnostic accuracy remains a major challenge.

Methods

We performed high-throughput proteomic analysis of ten paired BLCA and benign urothelial lesion (BUL) samples to identify ancillary proteomic markers for use in liquid-based cytology (LBC). Samples were analyzed mass spectrometry to identify differentially expressed proteins (DEP) between the two groups. A total of 4,839 proteins were identified and 111 DEP were confirmed as expressed at significantly different levels between the BLCA and BUL groups. Independent proteomic data generated from tissue samples (7,916 identified proteins and 784 DEP), along with comparative mRNA expression profiles from The Cancer Genome Atlas were analyzed for biomarker discovery. Six proteins, AHNAK, EPPK1, HSP90AB1, MYH14, OLFM4, and TUBB, were thereby identified as putative candidate and analyzed by immunostaining. To determine their immunocytochemical expression levels in LBC, protein expression was screened using data from The Human Protein Atlas and five proteins were finally selected for immunoreactivity validation in two independent LBC cohorts.

Results

These analyses confirmed AHNAK as a unique intracellular protein differing in immunohistochemical expression and subcellular localization between tumor and non-tumor cells. In conclusion, this study identified a new biomarker, AHNAK, applicable to discrimination between BLCA and BUL by LBC.

Conclusions

To our knowledge, the present study provides the first identification of a clinical biomarker for LBC based on in-depth proteomics.

Legal entity responsible for the study

Chnglim Hyun.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Case Summary

Leptomeningeal carcinomatosis (LMC) is a terminal event in advanced cancer, its incidence in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is increasing due to recent advances in systemic therapy and prolongation of survival.

Osimertinib is a third generation EGFR-tyrosine kinase inhibitor (TKI) with preclinical and early clinical studies showing activity against LMC resistant to previous TKI treatments and acquired T790M mutation.

We report a case of osimertinib in the treatment of LMC in a T790M-negative, EGFR-mutated NSCLC with significant clinical benefit and no toxicity.

Osimertinib is a potentially effective treatment for LMC associated with EGFR-mutated NSCLC regardless of T790M status and a well-tolerated treatment for poor performance status patients.

Background

The Indian sub-continent accounts for one-third of oral cancer burden in the world. Oral cancer and surgery can affect a person’s self-esteem and body image. The supportive care needs are many as these patients experience physical symptoms, social isolation and psychological distress during post-operative period.

Methods

The study was conducted at B.R.A.I.R.C.H, AIIMS, New Delhi. The data was collected by convenience sampling from 50 adults who underwent surgery for oral cancer during July 2017 to December 2017. A standardized self-structured supportive care need survey(SCNS) questionnaire assessed the perceived level of supportive care needs during hospital stay and at one month follow up. Descriptive and inferential statistics were used for data analysis. Ethical clearance was obtained from institutional ethics committee.

Results

80% patients were male. Majority of the patients underwent mandibulectomy (66%) modified neck dissection (60%) and regional flap reconstruction (56%). All of the post operative patients with oral cancer perceived need in Physical and daily living domain (100%), majority perceived need in Psychological domain (82%) and health system and information domain (56%) during hospital stay while majority of them perceived need in Physical and daily living domain (88.2%) and Psychological domain (55.7%) at one month follow up. The percentage of patients satisfied in patient care and support domain and health system and information domain during hospital stay were (46% and 28%) and one month follow up (58.1% and 51.1%). There was a significant decrease in the perceived level of need in Psychological domain of the post operative patients with oral cancer at one month follow up (26.92 + 7.33, 22.6 + 7.55) as compared to during hospital stay with p = 0.01,

Conclusions

The present study shows that there is need to support and care post-operative oral cancer patients in the physical and daily living domain and psychological domain even after their discharge from the hospital. Future studies with larger sample over extended period will yield much.

Legal entity responsible for the study

Neenumol Paulose.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

Head & neck cancer patients treated with radical/adjuvant radiotherapy suffer from weight loss, the cause of which can be multifactorial. In this study we have evaluated weight loss pattern in H&N cancer patients receiving either conventional or conformal chemoradiotherapy (CCRT)/adjuvant radiotherapy (RT) and to find out possible factors.

Methods

A retrospective study was done using data of already treated head & neck cancer patients. Inclusion criteria- 1) Primary site: oral cavity, oropharynx, larynx, & hypopharynx. 2) Treated with either radical CCRT(with Inj. Cisplatin) or adjuvant RT. Exclusion criteria- 1) palliative radiotherapy, 2)treatment gap >6 days. Basic parameters were collected, weight at beginning & at end of Radiotherapy noted. As general rule, Ryle’s tube insertion was done only when needed (difficulty to swallow liquid).

Results

160 patients’ data were collected: 80 patients- Conformal RT (40 patients radical CCRT & 40 patients adjuvant RT), 80 patients- Conventional RT (40 patients radical CCRT & 40 patients adjuvant RT). Only 5 patients (2 conformal CCRT & 3 conformal RT) out of total 160 patients gained weight during course of RT. Hence, 155 patients suffered weight loss. We compared variables with absolute weight loss of ≤ 5kg & >5kg using Chi square (χ2) test. Also, variables were compared with relative weight loss of ≤ 10% & >10%. The variables affecting both absolute and relative weight loss were initial low KPS status, use of conventional RT technique and use of chemotherapy & higher radiation dose (>60Gy). It was also found that ryle’s tube insertion was significantly more in patients with >5kg/>10% weight loss.Table: 312P

Variables affecting absolute and relative weight loss: χ2 Assessment (P Value) (* indicates significant)

Conclusions

Weight loss in H&N cancer patients during CCRT/RT is expected. Conformal RT (which corresponds to reduced treatment volume & toxicities), better KPS status can limit the extent of weight loss. Addition of chemotherapy and higher radiation dose (>60Gy) will increase weight loss. Ryle’s tube insertion as prophylaxis may be considered, specially in patients with expected weight loss >5kg/>10%.

Legal entity responsible for the study

Subhadip Das, Debarshi Lahiri, Syamsundar Mandal, Priyanka Biswas.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

SPARTAN was a global, phase 3 study that evaluated the efficacy and safety of APA vs placebo (PBO) in pts with high-risk nmCRPC, with significant improvement observed in the primary end point (metastasis-free survival; MFS) with APA (Smith, N Engl J Med 2018). Because studies of some targeted agents have demonstrated differences in outcomes among Asian (AS) compared with non-Asian (nAS) pts, we conducted a post hoc analysis of efficacy and safety of APA in the AS subpopulation of pts enrolled in SPARTAN.

Methods

SPARTAN included 1207 pts with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months. Pts were randomized 2:1 to APA (240 mg/d) or PBO added to androgen deprivation therapy. Pts treated in Japan, Taiwan, and South Korea were classified as AS. Baseline characteristics, MFS, PSA, and safety were evaluated for differences between AS and nAS pts.

Results

In the APA and PBO arms, respectively, 83 and 43 pts were AS; 723 and 358 were nAS. Most baseline characteristics were similar between AS and nAS pts; however, AS pts had lower body weight and were more likely to have N1 disease (APA arm) and Gleason score > 7 than nAS pts (Table). Median time from diagnosis to treatment (Tx) was shorter among AS pts than nAS pts. The magnitude of improvement in MFS with APA vs PBO was similar for AS (HR 0.29, P < 0.001) and nAS (HR 0.28, P < 0.0001) pts. A confirmed PSA response was observed in 82% vs 91% (AS vs nAS). No meaningful differences were observed in treatment-emergent adverse events (TEAEs) in AS vs nAS pts, except for rash (38% vs 22%). Tx discontinuations due to TEAEs were higher in Asian pts.

Conclusions

APA had a similar clinical benefit and manageable safety profile among AS and nAS pts with nmCRPC despite AS pts having higher risk characteristics at baseline.Table: 213O

Editorial acknowledgement

Writing assistance was provided by Brian Haas, PhD, of Parexel, and was funded by Janssen Global Services, LLC.

Clinical trial identification

NCT01946204.

Legal entity responsible for the study

Janssen R&D; Rosemary Long, RPh, MBA, Director, Global Medical Affairs Strategic Operations, Janssen Global Services, LLC.

Funding

Janssen Research & Development.

Disclosure

P. Mainwaring: Personal fees: XING Technologies P/L, Ipsen, Janssen, Novartis, Pfizer, Roche; Grants, personal fees: Merck, outside the submitted work; Patent: XING Technologies P/L pending. H. Uemura: Personal fees: Janssen; Personal fees: Astellas, Takeda, Sanofi, Bayer, AstraZenaca, outside the submitted work. A. Bhaumik, S. Cheng, A. Londhe, A. Lopez-Gitlitz: Employee: Janssen Research and Development; Holds stock: Johnson & Johnson. M. Smith: Reports grants, personal fees: Janssen, during the conduct of the study; Personal fees: Astellas, Bayer, outside the submitted work. All other authors have declared no conflicts of interest.