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Introduction HER2 mutations are found in 2% to 4% of non–small-cell lung cancer cases and are usually mutually exclusive with other genetic alterations. We screened a large cohort of patients from multiple institutions in Korea, described the characteristics of HER2-mutant cases, and reported on several patients who were treated with pan-HER inhibitors. Patients and Methods The study population consisted of 360 patients diagnosed with adenocarcinoma from 4 institutions in Korea from June 2015 to September 2016. Tissue specimens from all participants were screened by direct sequencing, and next-generation sequencing was conducted only on specimens that were positive in direct sequencing. HER2-targeted therapy, either poziotinib or afatinib, was orally administrated. Results Next-generation sequencing was conducted in 129 patients, and finally 29 (8.1%) patients with HER2 mutation were identified. Most patients were female (58.6%), had never smoked (70.0%), and had stage IV non–small-cell lung cancer (55.2%). For all patients, the histologic type was adenocarcinoma, with no coexisting EGFR or ALK alterations. The most common type of HER2 mutation (48.3%) was c.2326_2327insTGT in exon 20. A partial response was observed in 2 patients who received poziotinib and 1 patient who received afatinib. The main toxicities of the pan-HER inhibitors were nausea, diarrhea, and mucositis. Conclusion HER2 mutation was estimated at a frequency of approximately 8.1% in Korean patients with adenocarcinoma in the absence of known driver mutations. Because some of the HER2-mutant cases responded to poziotinib or afatinib, further studies are warranted.

Stage IIIA-N2 non-small cell lung cancer (NSCLC) shows prognostic heterogeneity. We investigated the prognostic relevance of the number of metastatic pN2 nodes in patients with IIIA-N2 NSCLC. The criteria for the number of pN2 used in this study were significantly associated with the survival outcomes after surgery and may improve the accuracy of prognostic prediction in this subgroup of patients.There have been controversies regarding the prognostic relevance of the number of positive N2 nodes in pathologic stage IIIA-N2 non-small-cell lung cancer (NSCLC). We examine prognosis of patients with pathologic stage IIIA-N2 with classifying the number of positive N2 nodes into subgroups.From January 1997 to December 2004, 250 patients were diagnosed with pathologic stage IIIA-N2 disease. All patients underwent mediastinal lymph node dissection. After excluding 44 patients with preoperative chemotherapy, incomplete resection, and postsurgical mortality, 206 patients were included in the analysis. Patients were classified according to the number of positive N2 lymph nodes (N2a: 1 [n = 83], N2b: 2-4 [n = 82], N2c: ≥ 5 [n = 41]), and its correlation with survival outcomes were investigated.With a median follow-up of 96.3 months, 5-year disease-free survival (DFS) was 27.2% (95% confidence interval [CI], 21.6-33.7), and 5-year overall survival (OS) was 37.7% (95% CI, 31.5-44.7) in all patients. The number of metastatic N2 lymph nodes was associated with DFS (P.001) and OS (P = .01). In the N2a, N2b, and N2c groups, 5-year DFS rates were 38%, 24%, and 5%, respectively, and 5-year OS rates were 47%, 35%, and 24%, respectively. In a multivariate analysis, the number of metastatic N2 lymph nodes was an independent prognostic factor for DFS and OS.Stratification of patients according to the number of metastatic N2 lymph nodes may improve the accuracy of prognostic prediction among patients with curatively resected stage IIIA-N2 NSCLC.

Background There have been conflicting findings regarding the efficacy of pemetrexed for lung cancer with anaplastic lymphoma kinase ( ALK ) rearrangement. This study was conducted to explore the benefits of pemetrexed in this patient group. Patients and Methods Among patients who had received pemetrexed therapy between January 2010 and March 2014 for advanced stage lung adenocarcinoma, cases were selected with a confirmed ALK rearrangement, epidermal growth factor receptor ( EGFR ) mutation, or Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation. Clinical outcomes resulting from the pemetrexed-based regimen were analyzed according to the genetic alteration. Results A total of 442 patients were enrolled, including 52 with ALK translocation, 188 with EGFR mutation, 34 with KRAS mutation, and 168 wild type patients. The mean age was 57 ± 11 years and women were predominant in the ALK -positive and EGFR mutant groups. Pemetrexed–platinum combination therapy was usually performed as first-line therapy, whereas pemetrexed monotherapy was usually used as second-line therapy and beyond. The response rate (RR) was greater in the ALK -positive group than in the other groups (26.9% vs. 12.8%, 8.8%, and 18.5%; P = .046). The median progression-free survival (PFS) of ALK -positive patients was longer than that of the others (7.8 months vs. 2.5, 2.3, and 2.9 months; P P Conclusion ALK -positive patients showed a greater RR and longer PFS with pemetrexed-based therapy than patients without ALK rearrangements, suggesting that pemetrexed should be preferentially considered for the treatment of ALK -positive lung adenocarcinoma when use of crizotinib is not feasible.

Background We investigated the characteristics of patients with epidermal growth factor receptor (EGFR)-mutant non–small-cell lung cancer (NSCLC) who had experienced isolated progression of bone metastases without aggravation of extraskeletal organs during EGFR-tyrosine kinase inhibitor (TKI) treatment. Materials and Methods We retrospectively reviewed the data from 870 patients with EGFR-mutant NSCLC treated with EGFR-TKI from 2004 to 2014. Of these patients, 71 (8.2%), who had undergone radiation therapy to bone metastases because of skeletal-related events, impending skeletal-related events, or medically uncontrolled bone pain, were selected and defined as having bone failure (BF). BFs were classified into 2 categories according to the presence of accompanying disease progression in extraskeletal organs: isolated BF (IBF) and non-IBF. Results Of the 71 BF patients, 33 (46.5%) experienced IBF without aggravation of disease in extraskeletal organs. IBF was more frequent in the clinical benefit group (responders and stable for ≥ 6 months) than in nonclinical benefit group (54.4% vs. 14.3%; P = .007). IBF was also more frequent in those with good performance status (82.5% vs. 42.9%; P = .005) and 19 deletion (68.4% vs. 35.7%; P = .024). Female sex, good performance status, and clinical benefit from TKI were more frequent in patients with IBF than in those with non-IBF (female sex, 69.7% vs. 44.7%; P = .034; Eastern Cooperative Oncology Group 0 or 1, 87.9% vs. 63.2%; P = .017; clinical benefit from TKI, 93.9% vs. 68.4%; P = .007). Clinical benefit from EGFR-TKI was an independent predictor of IBF (adjusted odds ratio, 6.647; 95% confidence interval, 1.328-33.262; P = .021). Patients with IBF tended to exhibit longer survival times from the initiation of the TKI (20.7 vs. 11.1 months; P = .2) and from the onset of BF (8.6 vs. 3.4 months; P = .186). Conclusion IBF without systemic disease progression frequently occurs in patients with clinical benefits from EGFR-TKI and is associated with better survival. This finding requires future studies to explore the differential activity of EGFR-TKI in the bones over time or in preference to other organs.

Tumor metastasis to the pituitary gland has been infrequently reported, and this is probably because only a small proportion of these patients are symptomatic. Most of the symptoms of this malady are related to diabetes insipidus. A 78-year-old man was diagnosed 2 years previously with stage IIIA adenocarcinoma of the lung and treated with sequential chemoradiation therapy and later with whole-brain radiation therapy because of newly developed brain metastasis; he was then admitted to our hospital with symptoms of polydipsia and polyuria. He was confirmed to have central diabetes insipidus that was caused by the pituitary metastasis from lung cancer. His symptoms resolved after treatment with desmopressin. Because of the rarity of this manifestation in lung cancer patients, we report on this case along with a brief review of the relevant literature.

We appreciate the interest in our report by Lin et al and the nice presentation of their experience about double primary cancer. Indeed, in the era of fluorine-18 (18F) fluorodeoxyglucose positron emission tomography (FDG-PET), it is not rare to encounter patients with multiple primary cancers, as we previously mentioned. Although multiple tumors in our reported case developed within the area that could be affected by the same carcinogen, we have often found the combination of double primary cancers in lung and colon, which could be explained by the high incidence of both tumors. We’d like to present one of our experiences similar to the case of Lin et al. Colon cancer was noted by 18FDG-PET during staging work-up for lung cancer in a 78-year-old man (Figures 1A and 1B). Endoscopic mucosal resection (EMR) for colon cancer was performed followed by operation of the lung through video-assisted thoracoscopy 3 days later (pathologic stage, IA). Endoscopic mucosal resection was chosen in this patient, considering advanced age, relatively poor performance, and early stage of colon cancer. Follow-up colonoscopy was performed 6 months later, which only showed fibrotic change on previous EMR site (Figure 1C). There is no clear guideline indicating which cancer should have priority regarding management in multiple primary cancers. Tumor-related complications such as bleeding, obstruction, perforation, and aggressiveness of the tumor itself would be the major considerations of decision. Lin et al described that they treated the colon cancer first because of the possibility of local progression. This decision might have considered the possibility of colon cancer perforation if surgery were to be delayed. Generally, treatment of lung cancer seems to precede because of its poorer prognosis than colon cancer. However, the decision was not difficult in our case because EMR was easily performed without interruption of surgical preparation of lung cancer. As Lin et al indicated, the possibility of multiple primary cancers should always be considered to provide optimal therapy in patients with multiple cancers at different sites.