UNASSIGNED: Alectinib, a highly potent, highly selective, brain-penetrant anaplastic lymphoma kinase (ALK) inhibitor is now the first line therapy for patients with metastatic ALK-positive non small cell lung cancer (NSCLC).
UNASSIGNED: We report a rare case of pneumoperitoneum following alectinib initiation for metastatic non small cell lung cancer in a 74-year-old African American female. Patient developed abdominal pain approximately 2 weeks after starting alectinib. She was hemodynamically stable, and imaging revealed pneumoperitoneum. Patient was successfully managed non-operatively.
UNASSIGNED: Gastrointestinal perforation presenting as pneumoperitoneum is a very rare complication of alectinib. To our knowledge our patient is only the second case to be reported in the literature since its approval. The complication is likely attributable to the rapid tumor regression in the gastrointestinal tract. Non-operative management should be attempted if possible.
UNASSIGNED: Oncologists should be aware of the risk of gastrointestinal perforation when initiating cytotoxic chemotherapy on patients with metastatic NSCLC. A multidisciplinary approach is critical in appropriately individualizing care in this patient population.

Immune checkpoint inhibitors (ICIs) are clinically used for treating advanced lung cancer, and some patients have achieved complete remission (CR) with ICI therapy in clinical trials. However, reports summarizing the clinical courses of such patients are limited. We report two cases of lung adenocarcinoma in which CR was achieved with first-line pembrolizumab monotherapy, and the therapeutic effect was maintained after treatment completion. Specific patients can achieve CR, even those who do not meet the previously reported predictors of treatment response other than high programmed death-ligand 1 expression. Thus, biomarkers that can accurately predict the clinical efficacy of ICIs are warranted.

Synchronous multiple primary lung cancers (SMPLC) should be distinguished from intrapulmonary metastasis to define the optimal treatment approach. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are typically mutually exclusive and the co-existence of both mutations is relatively rare. Herein, we report a case of SMPLC harboring each EGFR mutation and ALK rearrangement successfully treated with combination of osimertinib and alectinib. A combination of EGFR- and ALK-tyrosine kinase inhibitors could be an effective and tolerable therapeutic option for SMPLC with EGFR mutations and ALK rearrangement.

The development of resistance to tyrosine kinase inhibitors (TKIs) in metastatic non-small cell lung cancer (NSCLC) with oncogenic driver mutations highlights the challenge in improving the survival of these patients. The standard of care for ALK-rearranged advanced NSCLC refractory to various generations of ALK TKIs falls back to the use of chemotherapy and the prognosis remains poor. We report the case of a 41-year-old lady with an ALK-translocated metastatic lung adenocarcinoma, who demonstrated good response to an immune checkpoint inhibitor, atezolizumab in combination with bevacizumab and chemotherapy (pemetrexed and carboplatin), following disease progression on three generations of ALK TKIs. Six months into treatment, she continues to show improvement in her health-related quality of life and is tolerating treatment well. Our case suggests that this treatment regimen is a potential treatment option for TKI-refractory driver-mutated NSCLC.

Multiple EGFR-mutant and ALK-mutant lung cancers are rare, and standard treatment has not been established because of the small number of cases. A 79-year-old man was found to harbor nodular shadows in right S1, right S5, and left S3. He was surgically diagnosed with stage IIB (pT3N0M0) EGFR G719X-mutant lung adenocarcinoma in left S3 and stage IA1 (pT1aN0M0) ALK-mutant lung adenocarcinoma in right S5. Owing to the relapse of the EGFR-mutant adenocarcinoma, gefitinib treatment was commenced 3 months postoperatively. The tumor shrank temporarily; however, the nodular shadow in the right S1 and #3a lymph nodes were found to increase in size. He was diagnosed with adenosquamous carcinoma in right S1 and relapsing ALK-mutant adenocarcinoma in #3a lymph node. Gefitinib treatment was continued, but due to a renewed increase in the size of the #3a lymph node, the drug was changed to alectinib 16 months postoperatively. Subsequently, the EGFR-mutant adenocarcinomas were found to increase in left S1 despite the decrease in the #3a lymph node size. Nineteen months after the first surgery, the treatment was changed to gefitinib, and repeated treatment with this drug and alectinib administered every 2 months was continued. This approach enabled 39 months of progression-free survival, and no serious adverse events were observed.

Inflammatory myofibroblastic tumors (IMT) are rare soft tissue tumors of intermediate malignant potential with tendency for local recurrence. Although they can occur at all age groups, occurrence in infants is extremely unusual and their imaging characteristics are not well described. A 3-month-old female infant presented with gradually progressive abdominal distention without any fever or weight loss. She had a large ill-defined homogenous hypodense lesion of size 8.4 × 11.4 × 11.3 cm (APxTraxSag) in the abdomen showing mild delayed post contrast enhancement. She underwent exploratory laparotomy with gross total excision of mesenteric mass, histopathology of which was suggestive of IMT. She had recurrence within 6 months of complete resection with a well-defined heterogeneously enhancing lesion of size 1.8 × 1.8 × 2.3cm (APxTraxSag) in right paravesical region abutting the bladder without invasion with a similar lesion of size 4.4 × 2.1 × 3 cm (APxTraxSag) in left subdiaphragmatic region abutting superior surface of spleen (no invasion). Since, surgery in our patient would have entailed splenectomy and partial cystectomy, systemic therapy with ceritinib (anaplastic lymphoma kinase [ALK] inhibitor) was planned for her with which she had a near complete response after 2 months. A high index of suspicion is required to differentiate IMT from other common causes of mesenteric masses in children and role of radiologist is quintessential in this regard. Local recurrence with abutment but without invasion of surrounding structures points to the intermediate malignant pathology of IMT and may provide a clue to diagnosis. Systemic therapy is effective in patients who are ALK positive and destructive surgery should be avoided.

BACKGROUND: We report a case of sustained complete response in unfavorable cancer of unknown primary site (CUP) successfully treated with chemotherapy combining pembrolizumab, pemetrexed and platinum.
METHODS: A 66-year-old man was presented with weight loss and cough for 3 months. Contrast-enhanced computed tomography (CT) confirmed a mass in the superior anterior mediastinum and multiple enlarged mediastinal and axillary lymph nodes. Positron emission tomography-CT (PET-CT) showed abnormal uptake in the corresponding lesions. Histopathological analysis of the left axillary nodule revealed poorly differentiated adenocarcinoma. Immunohistochemistry showed the tumor cells were positive for cytokeratin 7 and thyroid transcription factor-1 and negative for cytokeratin 20. Thus, the patient was diagnosed as poorly differentiated adenocarcinoma of unknown primary, and treated as non-small-cell lung cancer. Additional genetic testing revealed the patient was negative for EGFR, ALK fluorescence in situ hybridization, ROS1, BRAF, and PD-L1 22C3 IHC with Tumor Proportion Score (TPS) was less than 1%. The patient received six cycles of pembrolizumab, platinum, and pemetrexed intravenously. Cisplatin was switched to carboplatin because of cisplatin nephrotoxicity in one course. PET-CT after six cycles showed all lesions disappeared; complete response was considered to have been achieved. Maintenance therapy of pembrolizumab and pemetrexed has been continued for 6 months after the induction therapies to prevent progressive disease. Complete response has been maintained.
CONCLUSIONS: Chemotherapy with pembrolizumab, platinum and pemetrexed could be valuable for treating unfavorable CUP.
CONCLUSIONS: Chemotherapy with pembrolizumab, platinum, and pemetrexed helped achieved sustained complete response in a patient with unfavorable CUP.

Although immune-checkpoint inhibitors (ICIs) have become an important choice of treatment for advanced NSCLC, recent reports show hyperprogressive disease (HPD) after ICI administration. The clinico-pathological features of HPD still remain unclear. Here we report a 65-year-old man with lung adenocarcinoma who abruptly presented HPD two days after pembrolizumab administration. The primary tumor increased in size from 40 mm to 57 mm on the chest HRCT. The patient died on day 37 after pembrolizumab administration. The autopsy demonstrated widespread progression of cancer cells into the alveolar spaces and lymphangitic carcinomatosis in the left lung, with plenty of bloody pleural effusion. We compared the pathohistology and immunohistochemical expression of PD-L1 between the pretreatment biopsy material and posttreatment autopsy materials, and found a change in PD-L1 expression which may be related to HPD. We also discuss the possibility of HPD, pseudoprogression, and interstitial lung disease when there is evidence of tumor growth or ground glass shadows on chest images after ICI treatment.

The present report describes the case of a 64-year-old woman with advanced lung adenocarcinoma expressing mutant epidermal growth factor receptor (EGFR). The patient developed follicular lymphoma during treatment with the EGFR-tyrosine kinase inhibitor afatinib. Standard immunochemotherapy for follicular lymphoma was introduced in addition to continuing treatment with afatinib for lung cancer. Immunochemotherapy was effective and improved the patient\'s performance status while afatinib controlled the progression of lung cancer. Our case study suggests that it is safe to introduce standard immunochemotherapy for patients who develop malignant lymphoma while continuing treatment with tyrosine kinase inhibitors for lung adenocarcinoma expressing mutant EGFR.

Although many strategies have been developed for non-small cell lung cancer (NSCLC), more secondary and further treatments are needed due to drug resistance or tumor recurrence. Apatinib is a novel oral antiangiogenic agent and in this study, we aim to investigate the clinical value of apatinib in heavily pretreated NSCLC. Here, we reported the characteristics, efficacy and adverse events of three patients treated with apatinib (500 mg/day). We also summarized the currently available evidence and ongoing clinical trials regarding the use of apatinib in NSCLC. Two cases of adenocarcinoma and one case of squamous cell carcinoma were treated with apatinib due to disease progression after previous treatments of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). All patients responded to apatinib rapidly and underwent drug resistance shortly afterwards. The patient with squamous cell carcinoma died of hemoptysis. Other adverse events were acceptable. All previous relevant studies were compared and showed similar results but a longer progression-free survival. Additionally, ongoing clinical trials were systematically searched and listed. In conclusion, apatinib shows some efficacy in heavily treated NSCLC and generally tolerable toxicity in non-squamous NSCLC. More solid evidence will be accessible in near future.