Background: While immune checkpoint inhibitor (ICI)-related pneumonitis (CIP) may relapse during or after steroid treatment, clinical factors associated with CIP relapse are unclear. This study explored risk factors potentially associated with CIP relapse. Methods: This single-center retrospective study included 1099 patients who received ICIs at our institution between April 2015 and March 2022. Among them, 39 patients who developed CIP and were treated with systemic steroids and tapered to prednisolone (PSL) ≤ 20 mg/day were analyzed. Patients were classified into relapse and non-relapse groups based on whether CIP recurred during or after steroid treatment. Patient characteristics, clinical features at onset, and treatment strategies were compared between the two groups. Results: Thirteen patients (33.3%) experienced relapse. Compared with the non-relapse group, the relapse group had a significantly higher proportion of non-smokers (30.8 vs. 3.3%, p = 0.035), a greater frequency of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 pneumonitis (92.3 vs. 53.8%, p = 0.029), and lower serum KL-6 levels (288 vs. 704 U/mL, p = 0.014). The relapse group also had a shorter duration of steroid therapy at the initial dose, ≥0.5 mg/kg/day, ≥15 mg/day, and ≥20 mg/day (p < 0.05) and lower cumulative steroid doses (1140 vs. 1902 mg, p = 0.015). Relapse tended to occur in patients with relatively mild pneumonitis who received lower steroid doses and shorter treatment durations. Conclusions: Non-smoking status, CTCAE Grade 2 pneumonitis, lower serum KL-6 levels, shorter duration of steroid therapy, and lower cumulative steroid dose were potentially associated with CIP relapse. Adequate steroid dosing and tapering may help prevent relapse.

Abstract Background The overall incidence of pituitary apoplexy among patients with pituitary adenoma ranges from 0.6% to 7.0%, although many cases likely go undiagnosed. Several precipitating factors have been identified, and a small number of case reports have suggested an association between immune checkpoint inhibitors and pituitary apoplexy, particularly in patients with preexisting adenoma. Moreover, the safety of immune checkpoint inhibitor rechallenge remains uncertain. Case presentation The patient was a 71-year-old woman with a recurrence of metastatic primary rectal melanoma. A pituitary tumor had been identified before initiation of systemic therapy. Following the second cycle of nivolumab plus ipilimumab, the patient developed headache, nausea, and vomiting, followed by decreased serum thyroid-stimulating hormone, adrenocorticotrophic hormone, and luteinizing hormone levels. These findings were consistent with evolving hypopituitarism. Contrast-enhanced magnetic resonance images revealed hemorrhage in the pituitary adenoma, suggesting pituitary apoplexy. Eight months after discontinuation of nivolumab plus ipilimumab, disease progression was noted, and nivolumab monotherapy was resumed. There was no recurrence of pituitary apoplexy during six cycles of nivolumab. Conclusions This case highlights that pituitary apoplexy can occur temporally after nivolumab plus ipilimumab treatment in patients with preexisting pituitary adenoma. Importantly, nivolumab monotherapy rechallenge under close monitoring may be feasible without recurrence of pituitary apoplexy.

Stage IV non-small cell lung carcinoma (NSCLC) with oligometastases is potentially curable by radical treatment. This study aimed to evaluate the efficacy and safety of chemoradiotherapy (CRT) for thoracic disease, including the primary lesion and lymph node metastases, combined with local consolidative therapy (LCT) for oligometastases. This was a multicenter Phase II trial for patients with Stage IV NSCLC with oligometastases for whom CRT for thoracic disease was feasible. The treatment procedures included CRT containing platinum-doublet for thoracic disease and LCT for oligometastases within 8 weeks of starting or completing CRT. The primary endpoint was the 2-year survival rate. We enrolled 19 patients between June 2016 and May 2020. The median age was 68 (range: 51–74) years. Twelve patients had adenocarcinoma, and 6 had squamous cell carcinoma. The metastasis sites included the brain, bone, adrenal gland, lung, and cervical lymph node (n = 9, 7, 2, 1, and 1, respectively). All patients completed CRT concurrently with LCT for all oligometastases. There were 11 partial responses, resulting in a response rate of 58

Background:There is no data of postoperative chemotherapy for patients with small cell lung cancer (SCLC) and interstitial pneumonia (IP). This study aimed to compare the prognosis of patients with SCLC with or without IP treated with postoperative chemotherapy. Methods:We conducted a retrospective study to compare the prognoses of patients with SCLC with or without IP treated with postoperative chemotherapy. Consecutive patients who underwent postoperative chemotherapy during 2011-2021 were included. IP and acute exacerbation of IP were diagnosed through discussion with respirologists, pathologists, and radiologists. The primary endpoint was the 3-year overall survival (OS) rate in patients with and without IP. Results:We included 34 patients with SCLC treated with postoperative chemotherapy. The median age was 72.5 years, and the median preoperative percentage of lung capacity to the predicted value was 92.4%. Ten patients were diagnosed with IP, including six patients with usual IP (UIP). Thirty of the 34 patients (88%) had clinical stage I; however, 7 patients (21%) experienced upstaging pathologically. The 3-year OS rate of all patients was 67%. The 3-year OS rates were 68% with IP, and 69% without IP. The 3-year OS rate was 50% in patients with UIP. The 3-year disease-free survival (DFS) rate was 54% in all patients, 57% without IP, and 36% with IP. The 3-year DFS rate was 17%. The 3-year DFS rate was 17% in the UIP subgroup. The frequency of adverse events equal to or higher than grade 3 was 65% in all patients, 60% with IP, and 67% without IP. Acute exacerbation of IP was not observed in patients with IP. Conclusions:The 3-year OS rate of patients with IP was comparable to that of without IP. Postoperative chemotherapy may be beneficial and tolerable by patients with SCLC, with or without IP. Further studies with larger cohorts are necessary to clarify the efficacy and safety of postoperative chemotherapy in patients with IP. This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN ID 000051612).

8623 Background: The phase 3 randomized trial comparing afatinib to chemotherapy in treatment-naïve non-small cell lung cancer (NSCLC) with a sensitizing uncommon epidermal growth factor receptor mutation ( EGFR ) (ACHILLES) met its primary endpoint at the interim analysis. This trial demonstrated statistically significant improvement in progression-free survival (PFS)with hazard ratio 0.421; 95% confidence interval (CI), 0.251–0.706; p = 0.0010). Here, we report the final updated survival data. Methods: In this open-label phase 3 study, treatment-naïve patients (n=109) with sensitizing uncommon EGFR mutant NSCLC were randomized 2:1 to receive oral afatinib (30 mg or 40 mg daily) or a combination of platinum (cisplatin 75 mg/m 2 or carboplatin AUC 5 or 6) and pemetrexed (500 mg/m 2 ), followed by pemetrexed maintenance therapy every 3 weeks. The primary endpoint was PFS according to RECIST 1.1 criteria. Overall survival (OS) was a secondary endpoint. Post-protocol treatment was administered at the physician's discretion. Results: As of the 2 December 2024 database lock, the median follow-up time was 33.6 months. Afatinib continued to improve PFS compared with chemotherapy (median, 10.8 months vs 7.0 months; HR [95% CI], 0.528 [0.338–0.827], p = 0.0052). The updated OS HR for afatinib compared to chemotherapy was 0.645 (95% CI, 0.359–1.160; p = 0.1433; 49/109 events, 44.9% maturity). The median OS was 45.0 months (range, 27.0–not estimated) in the afatinib group and 27.0 months (range, 15.9–50.4) in the chemotherapy group. The crossover rate to EGFR-TKI was 90.6% in the chemotherapy arm. Notably, the subgroup receiving a starting dose of 40mg afatinib and the subgroup of younger patients (< 75 years) showed a favorable OS HR (HR 0.371, 95%CI, 0.140–0.986; HR 0.422, 95%CI, 0.201–0.886). No new safety signals were observed in this update analysis. Conclusions: This final survival analysis confirmed the superiority of afatinib compared to chemotherapy for uncommon or compound EGFR mutation-positive advanced NSCLC. Clinical trial information: jRCTs 031180175 . Treatment arm n Median PFS, mo[95%CI] PFS HR[95%CI] Median OS, mo[95%CI] OS HR[95%CI] Afatinib All 73 10.8[8.6–13.2] 0.528[0.338–0.827] 45.0[27.0–NE] 0.645[0.359–1.160] Major uncommon(G719X, L861X, S768I/V) 44 10.0[7.2–11.4] 0.630[0.385–1.030] 42.0[17.8–NE] 0.878[0.470–1.639] Other uncommon 5 8.6[6.1–NR] 1.006[0.384–2.635] 37.8[27.0–NE] 0.814[0.237–2.794] Compound 24 15.5[9.1–21.0] 0.414[0.230–0.748] NR[30.2–NE] 0.358[0.132–0.972] Chemotherapy Platinum+Pemetrexed 36 7.0[4.7–8.3] - 27.0[15.9–50.4] -

PURPOSE:To our knowledge, the ACHILLES/TORG1834 trial is the first randomized study comparing afatinib and chemotherapy in patients with non-small cell lung cancer (NSCLC) harboring sensitizing uncommon epidermal growth factor receptor (EGFR) mutations. METHODS:This randomized, open-label study was performed at 51 Japanese institutions and recruited treatment-naïve patients with nonsquamous NSCLC with uncommon EGFR mutations, excluding exon 20 insertions and T790M mutations. Patients were randomly assigned 2:1 to receive afatinib (30 or 40 mg orally, at the treating physician's discretion) or a combination of platinum (cisplatin or carboplatin) and pemetrexed, followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), overall survival, and safety. A prespecified interim analysis was planned to provide clinically meaningful information promptly, along with a crossover recommendation if necessary. RESULTS:A total of 109 patients were enrolled between March 2019 and February 2023. In the interim analysis, the Data and Safety Monitoring Committee recommended early study termination. The median PFS was significantly longer in patients receiving afatinib than in those undergoing chemotherapy (10.6 v 5.7 months; hazard ratio, 0.421 [95% CI, 0.251 to 0.706]; P = .0010). ORRs to afatinib were similar across the overall population and among participants with major uncommon (G719X, L861Q, and S768I), compound, and other mutations (61.7%, 55.8%, 72.7%, and 60.0%, respectively). The most common grade 3 or higher adverse events were diarrhea, paronychia, and rash for afatinib, and appetite loss and nausea for chemotherapy. CONCLUSION:Afatinib should be considered the standard initial therapy for patients with NSCLC with sensitizing uncommon EGFR mutations.

We report a case in which a large amount of intraperitoneal free gas developed during endoscopic ultrasound-guided biliary drainage with the rendezvous technique. A 62-year-old woman presented with obstructive jaundice caused by a pancreatic head tumor. Endoscopic retrograde cholangiopancreatography was attempted but failed due to difficulty cannulating the bile duct. Consequently, endoscopic ultrasound-guided hepaticogastrostomy was performed using a fully covered metal stent. Subsequently, the rendezvous technique was employed to access the biliary system and perform an endoscopic sphincterotomy. Finally, a fully covered metal stent was placed transpapillary. Fluoroscopic imaging during the procedure revealed a large amount of gas between the liver and diaphragm. Despite the pneumoperitoneum, the patient experienced no abdominal pain or fever. One week later, a computed tomography scan confirmed the disappearance of free air in the intraperitoneal cavity. The patient's subsequent clinical course remained uneventful, and she was discharged from the hospital. This case highlights the potential for pneumoperitoneum to develop during endoscopic ultrasound-guided biliary drainage, particularly when using the rendezvous technique. It is crucial to differentiate this finding from gastrointestinal perforation based on clinical presentation and imaging features.

Humoral hypercalcemia of malignancy (HHM) is often reported in cancers derived from the squamous epithelium; however, there are very few reports of HHM in patients with gallbladder cancer. We report a case of a parathyroid hormone-related protein (PTHrP)-producing gallbladder cancer presenting with HHM. A 43-year-old woman presented with appetite loss, nausea, and brown-colored urine. Blood tests revealed that she had hypercalcemia, high serum bilirubin, and high serum parathyroid hormone. Contrast-enhanced computed tomography revealed a gallbladder tumor, liver metastasis, and bile duct obstruction caused by the gallbladder tumor in the hilar region. No bone metastasis was observed. Endoscopic retrograde cholangiopancreatography revealed pancreaticobiliary maljunction. Metal biliary stents were placed, and a transpapillary biopsy of the gallbladder tumor revealed a pathological diagnosis of adenocarcinoma. The patient was diagnosed with HHM due to gallbladder cancer with liver metastasis. Although her hypercalcemia and jaundice improved, her appetite loss and nausea did not improve. Subsequently, the patient developed disseminated intravascular coagulation, and her general condition gradually deteriorated. Due to her poor general condition, chemotherapy could not be administered. The patient died six weeks after visiting our hospital. Although rare, some gallbladder cancers cause HHM due to PTHrP production.

1502 Background: To determine optimal treatment in older cancer patients, it is recommended to conduct a geriatric assessment (GA) before chemotherapy. The ENSURE-GA study, which focused on patients aged 75 and older with non-small cell lung cancer (NSCLC), reported that the implementation of GA not only enhanced patient satisfaction with regards to communication with their physicians, but also improve the patients’ quality of life. Additionally, we assessed whether GA could improve overall survival and serve as a predictor for severe adverse events. Methods: Patients aged ≥75 with NSCLC who were unable undergo radical treatment were enrolled. All patients underwent a standardized GA before treatment. The participating institutions were cluster-randomized into either intervention group or control group. For the intervention group, GA summaries and recommendations for GA-guided interventions were provided to guide physicians in selecting treatments and interventions. The control group did not provide physicians with GA summaries. Geriatric 8 (G8) and CARG scores were calculated at enrollment, and we investigated whether adverse events during a 3-month follow-up could be predicted. Results: Between 2019 and 2022, 1,021 patients were enrolled from 78 institutions in Japan. No significant differences were observed in patient characteristics or for GA domains between intervention and control groups. Additionally, there were no significant differences seen in 1-year overall survival (20.7m vs 18.8m, p = 0.414), or the incidence of grade 3 or higher adverse events in patients treated with medical treatment (36.8% vs 38.1%, p = 0.732). The ROC curve for G8 regarding the occurrence of grade 3 or higher adverse events in cases receiving cytotoxic chemotherapy yielded an AUC of 0.525, indicating no discriminatory ability. Furthermore, there was no difference in the incidence of adverse events between low-risk and high-risk patients based on the CARG score. Conclusions: The implementation of GA and interventions based on its results enhances patient satisfaction. However, additional studies are needed before incorporating GA into an adverse event prediction system. Developing risk scoring tools specific to cancer types and races may prove useful. Clinical trial information: UMIN0000037590 .

A 70-year-old woman presented to our hospital with abdominal discomfort. Gastrointestinal endoscopy revealed an ampullary tumor, while a biopsy revealed a pathological diagnosis of adenocarcinoma. No distant metastases were observed and neoadjuvant chemotherapy and surgical resection were planned. Shortly thereafter, she developed obstructive jaundice due to the ampullary carcinoma. The patient underwent endoscopic retrograde cholangiopancreatography, during which a straight plastic stent was placed in the bile duct. The patient was discharged without complications. Neoadjuvant chemotherapy was initiated. Two months later, she was readmitted for surgery while asymptomatic. Endoscopic retrograde cholangiopancreatography was scheduled to replace the stent with a nasobiliary drainage tube for the surgery. Endoscopic imaging revealed that the proximal end of the stent had penetrated the duodenum on the oral side of the ampullary carcinoma. The distal end of the stent was grasped with forceps and the stent was successfully removed. A catheter was inserted into the bile duct orifice and cholangiography was performed, which revealed that the distal bile duct and the duodenum had formed a fistula. A guidewire was placed in the bile duct via the papilla and a nasobiliary drainage tube was placed. After endoscopic retrograde cholangiopancreatography, the patient exhibited smooth progress without issue. Pancreaticoduodenectomy was performed on the fourth day after the nasobiliary drainage tube placement, and the patient's postoperative course was uneventful. The proximal end of a biliary stent penetrating the duodenal wall is an infrequent phenomenon. This case report highlights a rare but noteworthy adverse event associated with straight biliary plastic stent placement.

8613 Background: Dual inhibition of the EGFR/VEGF pathways has demonstrated superior efficacy with 1st generation EGFR tyrosine kinase inhibitor (TKI) in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. This study aims to evaluate the efficacy and safety of combining osimertinib (Osi), a 3rd generation TKI considered the standard of care, with ramucirumab (Ram). We have previously shown the result of progression free survival (PFS) as a primary endpoint, the median PFS was 20.0 months for Osi+Ram and 24.0 months for Osi, hazard ratio of 1.054 (95% CI 0.674-1.648). In further analyses, we aimed to examine the effects of this combination therapy on overall survival (OS). Methods: Previously untreated EGFR mutation-positive advanced non-squamous NSCLC patients with a performance status of 0 or 1 were eligible. Asymptomatic and/or treated brain metastases were included. Eligible patients were randomized at a 1:1 ratio to receive Osi (80mg) every day either without or with Ram (10mg/kg) every 2 weeks until disease progression or unacceptable toxicity, stratified according to gender and the type of EGFR mutation (exon 19 deletion, L858R). The primary endpoint was PFS assessed by the independent blinded radiologic reviewer. Secondary endpoints included PFS assessed locally, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), OS and safety. Results: Between November 2018 and April 2020, 122 patients (Osi+Ram: 59, Osi: 63) were enrolled. The patients' characteristics were well balanced. 59% were females, and 61% had an exon 19 deletion. Median age was 70 years old (range, 29-86). With a median follow up of 36.0 months, the median OS was 43.4 months (95% CI 36.5-N.R.) for Osi+Ram and N.R. (95% CI 41.3-N.R.) for Osi, resulting in a hazard ratio of 1.159 (95% CI 0.645-2.083, p = 0.62). Median treatment duration for Ram was 140 (14-1239) days. Ram was discontinued in 45 patients (76%) by the treatment related adverse effects. Common reasons for Ram discontinuation were platelet count decreased (n=14), proteinuria (n=12), neutrophil count decreased (n=11), pneumonitis (n=3), bleeding (n=3) and infection (n=3). Pneumonitis was observed in 16% in Osi, 9% in Osi+Ram, with grade 3 observed in 2% of both arms. Conclusions: Both treatment arms demonstrated sustained OS over 43 months. However, this study did not show an advantage of biweekly Ram administration with Osi in terms of PFS and OS. Notably, there was surpassed increase of early discontinuation of Ram due to higher adverse events. Clinical trial information: 2080224085 .

8588 Background: The ACHILLES/TORG1834 trial is the first randomized phase 3 study, demonstrating the superiority of afatinib to chemotherapy in terms of progression-free survival (PFS) as a primary endpoint in sensitizing uncommon epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) (the hazard ratio [HR] of PFS was 0.422, p=0.0007). This trial was early terminated due to efficacy according to the recommendation by the data and safety monitoring committee. Here we report the overall survival (OS) result, subgroup analysis of PFS, and the response data according to detailed mutation status at the primary analysis. Methods: In this open-label phase III study, treatment-naïve patients (n=109) with sensitizing uncommon EGFR mutant NSCLC were randomized 2:1 to oral afatinib (30 mg or 40 mg daily) or the combination of platinum (cisplatin 75 mg/m 2 or carboplatin AUC 5 or 6) and pemetrexed (500 mg/m 2 ), followed by pemetrexed maintenance therapy every 3 weeks. The primary endpoint was PFS per RECIST 1.1. The secondary endpoints included objective response rate (ORR), time to treatment failure (TTF), and OS. Results: Median follow-up time was 12.5 (range, 0 to 43.5) months. The OS HR of afatinib compared to chemotherapy was 0.989 (95% confidence interval [CI], 0.457 to 2.141; p=0.9772; 29/109 events, 26.6% maturity). Median OS was not reached in either population. All subgroups of PFS did better in the afatinib arm. In the subgroup regarding the starting dose of afatinib, the PFS HR in the 40mg afatinib arm (HR 0.128, 95%CI, 0.050 to 0.327) were favorable compared to that in the 30mg afatinib arm (HR 0.704, 95%CI, 0.352 to 1.406). In this subgroup, there were several differences in the baseline characteristics regarding age and gender. The detail of ORR and PFS according to mutations status was shown in the table. The safety profiles in both arms were consistent compared to previous reports. Conclusions: A consistent PFS benefit of afatinib over platinum-doublet chemotherapy was shown regardless the mutation status in patients with uncommon or compound EGFR mutations. The OS data were immature, and further follow-up will be warranted. Clinical trial information: 031180175 . [Table: see text]

Comparison of the background between this study and the PACIFIC study

AbstractPurpose:Concurrent chemoradiotherapy (CCRT) followed by durvalumab consolidation for up to 12 months is the standard of care for patients with unresectable stage III non–small cell lung cancer (NSCLC). However, exactly when to initiate durvalumab therapy after chemoradiation completion remains unknown. We evaluated the efficacy and safety of durvalumab, administered immediately after CCRT completion, for patients with unresectable stage III NSCLC.Patients and Methods:This study was a prospective, single-arm, open-label phase II clinical trial. Patients without disease progression after definitive CCRT (two cycles of platinum-based doublet chemotherapy with 60 Gy/30 Fr radiotherapy) received durvalumab (every 2 weeks for up to 12 months) from the next day (up to 5 days) after the final radiation dose. The primary endpoint was the 1-year progression-free survival (PFS) from registration before the start of CCRT.Results:From January 2020 to August 2020, 47 of 50 enrolled patients were evaluable for treatment efficacy and safety. The 1-year PFS from registration was 75.0% [60% confidence interval (CI), 69.0–80.0 and 95% CI, 59.4–85.3]. The objective response rate throughout the study treatment and median PFS from registration were 78.7% and 14.2 months (95% CI, 13.4 to not reached), respectively. Grade 3/4 pneumonitis and febrile neutropenia were each 4.3%.Conclusions:Our study met the primary endpoint. The incidence of pneumonitis was similar to that of a Japanese subset in the PACIFIC study. Our data support the efficacy and safety of durvalumab administered immediately after the completion of CCRT for patients with unresectable stage III NSCLC.

BackgroundEfficacy of necitumumab [recombinant human monoclonal antibody that blocks the ligand binding epidermal growth factor receptor (EGFR)] in patients with squamous (SQ) non-small-cell lung cancer (NSCLC) has been confirmed in two randomized clinical trials (SQUIRE and JFCM). This study evaluated the association between efficacy and initial skin toxicity with necitumumab treatment by analyzing pooled data from two clinical trials (SQUIRE and JFCM).Materials and methodsData of 635 patients with SQ-NSCLC (intent-to-treat population) treated with necitumumab plus gemcitabine and cisplatin (N + GC) were pooled from two clinical trials (SQUIRE and JFCM). The relationship between skin toxicities developed by the end of the second cycle and efficacy was evaluated. Efficacy endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Univariate and multivariate analyses were carried out for these endpoints.ResultsOS and ORR were associated with skin toxicity, whereas PFS was not. Patients with grade ≥2 or grade 1 skin toxicity had significantly longer OS compared to patients without skin toxicity (grade 0) in the N + GC group [median = 15.0 (grade ≥2); 12.7 (grade 1); 9.4 (grade 0) months; hazard ratio (HR) = 0.51 (grade ≥2 to grade 0); 95% confidence interval (CI) 0.40-0.64, P < 0.001 and HR = 0.64 (grade 1 to grade 0); 95% CI 0.52-0.80, P < 0.001]. In multivariate analysis, OS was significantly associated with skin toxicity.ConclusionsA significant association was found between necitumumab-induced skin toxicity and efficacy. These results are consistent with the previously reported association between other EGFR inhibitors-induced skin toxicity and efficacy.

Surgery and radiation to the lung, and chemotherapy of cytotoxic, molecular targeted agents and immune check point inhibitors (ICI) sometimes cause acute lung injury with high lethality rate. The risk factors for it include existing lung lesions, and interstitial lung diseases (ILD), including idiopathic pulmonary fibrosis (IPF), are especially important. The prediction of the occurrence, however, is difficult because ILD factors and agents at high risk are not fully understood. Anti-fibrotic agents, pirfenidone and nintedanib, are under investigation for their efficacy in reducing the occurrence of chemotherapy-induced acute exacerbation of IPF. Besides, mechanisms underlying lung injury may be different among cytotoxic, molecular targeted agents and ICI. For example, lung injury with mTOR inhibitors usually is not so serious that the agents can be continued. Cases of acute onset of tuberculosis and non-tuberculous mycobacteriosis during the use of ICI are reported, and speculated mechanisms for them includes IRIS (immune reconstitution inflammatory syndrome). On such cases, risk evaluation prior to therapy, close monitoring and prompt differential diagnosis followed by adequate treatment surely ameliorate the situation. The problems and possible solutions will be discussed.

BACKGROUND:Bevacizumab with platinum doublet therapy including paclitaxel + carboplatin improves the survival of patients with non-squamous non-small cell lung cancer. However, in a previous trial (CA031), paclitaxel + carboplatin led to Grade > 3 neutropenia in a Japanese population. Nanoparticle albumin-bound paclitaxel exhibits an improved toxicity profile. We evaluated the safety, dosage and response rate of the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination in a Japanese population. METHODS:Chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer were included. The dosage schedule was established in the Phase I trial as follows: 4-6 cycles of carboplatin (area under the concentration-time curve = 6 on Day 1) + nanoparticle albumin-bound paclitaxel (100 mg/m2 on Days 1, 8 and 15) + bevacizumab (15 mg/kg on Day 1), followed by maintenance therapy (nanoparticle albumin-bound paclitaxel + bevacizumab). The response rate and presence of adverse effects were evaluated in the Phase II trial. RESULTS:The overall response rate was 56.5% (90% confidence interval: 44.5-68.5), and 93% of patients (43/46) showed tumor shrinkage or maintained a stable disease course. The primary endpoint was achieved. At the median follow-up duration of 42 months, the median overall survival was 18.9 (range: 10.5-32.4) months. The most frequently observed Grade ≥ 3 adverse effects were neutropenia (72%), leukopenia (50%) and anemia (30%). CONCLUSIONS:All adverse effects were manageable and none resulted in patient death. In conclusion, the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination is favorable and well tolerated in Japanese patients as first-line treatment for advanced non-squamous non-small cell lung cancer.

Background Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited. Methods We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and “others”. H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx. Results We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and “others”, thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC. Conclusions This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.

Introduction: Stage IV non-small cell lung carcinoma (NSCLC) with oligometastases is potentially curable by radical treatment. This study aimed to evaluate the efficacy and safety of chemoradiotherapy (CRT) for thoracic disease, including the primary lesion and lymph node metastases, combined with local consolidative therapy (LCT) for oligometastases. Methods: This was a multicenter Phase II trial for patients with Stage IV NSCLC with oligometastases for whom CRT for thoracic disease was feasible. The treatment procedures included CRT containing platinum-doublet for thoracic disease and LCT for oligometastases within 8 weeks of starting or completing CRT. The primary endpoint was the 2-year survival rate. Results: We enrolled 19 patients between June 2016 and May 2020. The median age was 68 (range: 51–74) years. Twelve patients had adenocarcinoma, and 6 had squamous cell carcinoma. The metastasis sites included the brain, bone, adrenal gland, lung, and cervical lymph node (n = 9, 7, 2, 1, and 1, respectively). All patients completed CRT concurrently with LCT for all oligometastases. There were 11 partial responses, resulting in a response rate of 58% (95% confidence interval [CI]: 33.5–79.7%). Median progression-free survival and overall survival were 8.6 (95% CI: 7.0–10.2) and 42.1 (80% CI: 13.6–not reached) months, respectively. The 2-year survival rate was 68.4% (80% CI: 52.6–79.9%). Fourteen patients (74%) showed progression with newly observed lesions. There were no severe adverse events, and toxicities were tolerable. Conclusion: Chemotherapy in combination with aggressive LCT for NSCLC with oligometastases might extend survival and achieve local control. Clinical trial registration: University Hospital Medical Information Network, Japan (protocol identification number: UMIN000022431, first registration date: 01/JUN/2016)