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In 1995, Ginsberg et al. compared lobectomy with limited resection including segmentectomy and wide-wedge resection for stage I lung cancer in a randomized controlled trial and found that limited resection should not be applied to otherwise healthy patients with clinical stage IA lung cancer who can tolerate lobectomy. However, recent advances in diagnostic technology have improved the precision of detecting early-stage and small lung cancers. Therefore, whether radical segmentectomy, anatomical segmentectomy with hilar and mediastinal lymph node dissection (that is more valuable than wedge resection in terms of oncological aspects) and lobectomy are comparable in terms of curative intent for patients with early-stage non-small cell lung cancer (NSCLC) remains controversial. The role of segmentectomy differs according to tumor or patient characteristics. High resolution computed tomography findings of tumor size, location, and the presence or ratio of a ground glass opacity (GGO) component and the maximum of standardized uptake value on fluorine-18-2-deoxy- d -glucose positron emission tomography are important for selecting surgical procedures because the malignant potential of even early-stage NSCLC is variable. The ongoing JCOG0802/WJOG4607L, JCOG1211, and CALGB140503 trials will disclose the influence of segmentectomy for patients with early-staged NSCLCs that are small peripheral tumors based on preoperative high-resolution computed tomography findings about preserved pulmonary function and long-term prognosis. Segmentectomy is a key surgical procedure that general thoracic surgeons will need to master considering that it can be converted to lobectomy if the surgical margin is insufficient or lymph node metastasis is intraoperatively confirmed.

Chemotherapy for patients with advanced oesophageal squamous cell carcinoma offers poor long-term survival prospects. We report the final analysis from our study of the immune checkpoint PD-1 inhibitor nivolumab versus chemotherapy in patients with previously treated advanced oesophageal squamous cell carcinoma. We did a multicentre, randomised, open-label, phase 3 trial (ATTRACTION-3) at 90 hospitals and cancer centres in Denmark, Germany, Italy, Japan, South Korea, Taiwan, the UK, and the USA. We enrolled patients aged 20 years and older with unresectable advanced or recurrent oesophageal squamous cell carcinoma (regardless of PD-L1 expression), at least one measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a baseline Eastern Cooperative Oncology Group performance status of 0–1, and who were refractory or intolerant to one previous fluoropyrimidine-based and platinum-based chemotherapy and had a life expectancy of at least 3 months. Patients were randomly assigned (1:1) to either nivolumab (240 mg for 30 min every 2 weeks) or investigator's choice of chemotherapy (paclitaxel 100 mg/m2 for at least 60 min once per week for 6 weeks then 1 week off; or docetaxel 75 mg/m2 for at least 60 min every 3 weeks), all given intravenously. Treatment continued until disease progression assessed by the investigator per RECIST version 1.1 or unacceptable toxicity. Randomisation was done using an interactive web response system with a block size of four and stratified according to geographical region (Japan vs rest of the world), number of organs with metastases, and PD-L1 expression. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival, defined as the time from randomisation until death from any cause, in the intention-to-treat population that included all randomly assigned patients. Safety was assessed in all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT02569242, and follow-up for long-term outcomes is ongoing. Between Jan 7, 2016, and May 25, 2017, we assigned 419 patients to treatment: 210 to nivolumab and 209 to chemotherapy. At the time of data cutoff on Nov 12, 2018, median follow-up for overall survival was 10·5 months (IQR 4·5–19·0) in the nivolumab group and 8·0 months (4·6–15·2) in the chemotherapy group. At a minimum follow-up time (ie, time from random assignment of the last patient to data cutoff) of 17·6 months, overall survival was significantly improved in the nivolumab group compared with the chemotherapy group (median 10·9 months, 95% CI 9·2–13·3 vs 8·4 months, 7·2–9·9; hazard ratio for death 0·77, 95% CI 0·62–0·96; p=0·019). 38 (18%) of 209 patients in the nivolumab group had grade 3 or 4 treatment-related adverse events compared with 131 (63%) of 208 patients in the chemotherapy group. The most frequent grade 3 or 4 treatment-related adverse events were anaemia (four [2%]) in the nivolumab group and decreased neutrophil count (59 [28%]) in the chemotherapy group. Five deaths were deemed treatment-related: two in the nivolumab group (one each of interstitial lung disease and pneumonitis) and three in the chemotherapy group (one each of pneumonia, spinal cord abscess, and interstitial lung disease). Nivolumab was associated with a significant improvement in overall survivaland a favourable safety profile compared with chemotherapy in previously treated patients with advanced oesophageal squamous cell carcinoma, and might represent a new standard second-line treatment option for these patients. ONO Pharmaceutical Company and Bristol-Myers Squibb.

PurposeThis study compares the sensitivity of dedicated breast positron emission tomography (DbPET) and whole body positron emission tomography (WBPET) in detecting invasive breast cancer based on tumor size and biology. Further, we explored the relationship between maximum standardized uptake value (SUVmax) of DbPET and biological features of the tumor.MethodsA total of 639 invasive breast cancer lesions subjected to both DbPET and WBPET before surgery, between January 2016 and May 2019, were included in the study. The sensitivity of DbPET and WBPET in detection and the biology of the tumor according to the clinicopathological features were retrospectively evaluated.ResultsThe overall sensitivity of DbPET was higher than that of WBPET (91.4% vs. 80.3%, p < 0.001). Subcentimetric tumors were significant (80.9% vs. 54.3%, p < 0.001). Regardless of the nuclear grade, DbPET could detect more lesions than WBPET. The SUVmax was positively correlated with tumor size (R = 0.395, p < 0.001) and the nuclear grade (p < 0.001). Luminal A-like breast cancer had significantly lower SUVmax values than the other subtypes (p < 0.001).ConclusionsDbPET is superior to WBPET in the detection of subcentimetric, low-grade breast cancers. Further, by using SUVmax, DbPET can distinguish luminal A-like breast cancer from the other subtypes.

BackgroundSegmentectomy has been increasingly used for lung cancer treatment, however there are very limited data evaluating the postoperative pulmonary function of patients treated with complex segmentectomy. We evaluated the postoperative pulmonary function of patients who underwent complex segmentectomy compared with simple segmentectomy, wedge resection, and lobectomy.MethodsWe retrospectively analyzed data from 580 patients who underwent surgical resection. The patients were divided into four groups: complex segmentectomy (n = 135), simple segmentectomy (n = 83), wedge resection (n = 89), and lobectomy (n = 273). Functional testing included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and predicted diffusing capacity of the lung for carbon monoxide (%DLCO) measured preoperatively and at 12 months after surgery.ResultsDuring the postoperative course, the complex segmentectomy and simple segmentectomy groups showed a comparable course of pulmonary function. The complex segmentectomy group significantly preserved pulmonary function compared with the lobectomy group (FVC, p = 0.017; FEV1, p = 0.010; %DLCO, p = 0.0043). A similar trend was observed even when restricted to lung diseases in the right upper lobe. On the other hand, when comparing complex segmentectomy with wedge resection, complex segmentectomy showed a trend that was more disadvantageous than wedge resection, but this difference was not significant (FVC, p = 0.19; FEV1, p = 0.40; %DLCO, p = 0.96).ConclusionsComplex segmentectomy showed comparable postoperative pulmonary functions as simple segmentectomy. Complex segmentectomy could preserve pulmonary function significantly compared with lobectomy and did not result in significant loss compared with wedge resection.

In the open‐label, phase III CheckMate 816 study (NCT02998528), neoadjuvant nivolumab plus chemotherapy demonstrated statistically significant improvements in event‐free survival (EFS) and pathological complete response (pCR) versus chemotherapy alone in patients with resectable non‐small‐cell lung cancer (NSCLC). Here we report efficacy and safety outcomes in the Japanese subpopulation. Patients with stage IB–IIIA, resectable NSCLC were randomized 1:1 to nivolumab plus chemotherapy or chemotherapy alone for three cycles before undergoing definitive surgery within 6 weeks of completing neoadjuvant treatment. The primary end‐points (EFS and pCR) and safety were assessed in patients enrolled at 16 centers in Japan. Of the Japanese patients randomized, 93.9% (31/33) in the nivolumab plus chemotherapy arm and 82.9% (29/35) in the chemotherapy arm underwent surgery. At 21.5 months' minimum follow‐up, median EFS was 30.6 months (95% confidence interval [CI], 16.8–not reached [NR]) with nivolumab plus chemotherapy versus 19.6 months (95% CI, 8.5–NR) with chemotherapy; hazard ratio, 0.60 (95% CI, 0.30–1.24). The pCR rate was 30.3% (95% CI, 15.6–48.7) versus 5.7% (95% CI, 0.7–19.2), respectively; odds ratio, 7.17 (95% CI, 1.44–35.85). Grade 3/4 treatment‐related adverse events were reported in 59.4% versus 42.9% of patients, respectively, with no new safety signals identified. Neoadjuvant nivolumab plus chemotherapy resulted in longer EFS and a higher pCR rate versus chemotherapy alone in Japanese patients, consistent with findings in the global population. These data support nivolumab plus chemotherapy as a neoadjuvant treatment option in Japanese patients with resectable NSCLC. We report efficacy and safety outcomes in the Japanese subpopulation of patients with resectable non‐small‐cell lung cancer (NSCLC) in the global, randomized, open‐label, phase III CheckMate 816 study (NCT02998528). At a minimum follow‐up of 21.5 months, neoadjuvant nivolumab plus chemotherapy versus chemotherapy alone resulted in longer event‐free survival (median, 30.6 [95% CI, 16.8–not reached] vs. 19.6 [95% CI, 8.5–not reached] months) and a higher pathological complete response rate (30.3% [95% CI, 15.6–48.7] vs. 5.7% [95% CI, 0.7–19.2]) in Japanese patients, consistent with findings in the global population; no new safety signals were identified. Results support the use of neoadjuvant nivolumab plus chemotherapy in Japanese patients with resectable NSCLC.

BackgroundThis study aimed to investigate the efficacy of the Deauville criteria (a 5-point visual scale criteria) in assessing the accumulation of [18F]-fluoro-2-deoxy-d-glucose (FDG) on positron-emission tomography (PET)/computed tomography (CT) for predicting prognosis of early-stage lung adenocarcinoma and selecting candidates for sublobar resection.MethodsThis retrospective study included 648 patients undergoing curative resection for clinical N0 lung adenocarcinoma with a whole tumor size of 3 cm or smaller between April 2007 and March 2019. Accumulations of the FDG on PET/CT scans were scored using the Deauville criteria (Deauville score), and correlations between the Deauville score and prognosis were analyzed.ResultsThe recurrence-free survival (RFS) was significantly better for the patients with a Deauville score of 1 or 2 (n = 415, 5-year RFS, 92.6%) than for those with a score of 3 (n = 82, 5-year RFS, 72.7%; P < 0.001) or a score of 4 or 5 (n = 151, RFS, 70.8%; P < 0.001). The RFS did not differ significantly among the patients with Deauville scores of 1 and 2 who underwent wedge resection (n = 102, 5-year RFS, 90.5%), segmentectomy (n = 188, RFS, 95.1%; P = 0.355), and lobectomy (n = 125, RFS, 91.1%; P = 0.462).ConclusionThe 5-point-scale evaluation of FDG accumulation on PET/CT was useful in predicting the prognosis for patients with early-stage lung adenocarcinoma. Lung adenocarcinoma patients with a whole tumor size of 3 cm or smaller and a Deauville score of 1 or 2 can be candidates for sublobar resection.

Emerging evidence indicates that small RNAs, including microRNAs (miRNAs) and their isoforms (isomiRs), and transfer RNA fragments (tRFs), are differently expressed in breast cancer (BC) and can be detected in blood circulation. Circulating small RNAs and small RNAs in extracellular vesicles (EVs) have emerged as ideal markers in small RNA‐based applications for cancer detection. In this study, we first undertook small RNA sequencing to assess the expression of circulating small RNAs in the serum of BC patients and cancer‐free individuals (controls). Expression of 3 small RNAs, namely isomiR of miR‐21‐5p (3′ addition C), miR‐23a‐3p and tRF‐Lys (TTT), was significantly higher in BC samples and was validated by small RNA sequencing in an independent cohort. Our constructed model using 3 small RNAs showed high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.92 and discriminated early‐stage BCs at stage 0 from control. To test the possibility that these small RNAs are released from cancer cells, we next examined EVs from the serum of BC patients and controls. Two of the 3 candidate small RNAs were identified, and shown to be abundant in EVs of BC patients. Interestingly, these 2 small RNAs are also more abundantly detected in culture media of breast cancer cell lines (MCF‐7 and MDA‐MB‐231). The same tendency in selective elevation seen in total serum, serum EV, and EV derived from cell culture media could indicate the efficiency of this model using total serum of patients. These findings indicate that small RNAs serve as significant biomarkers for BC detection. EV small RNA in breast cancer can be found in serum small RNA biomarker.

In this report, a hand-held impulse-radar breast cancer detector is presented and the detectability of malignant breast tumors is demonstrated in the clinical test at Hiroshima University Hospital, Hiroshima, Japan. The core functional parts of the detector consist of 65-nm technology complementary metal-oxide-semiconductor (CMOS) integrated circuits covering the ultrawideband width from 3.1 to 10.6 GHz, which enable the generation and transmission of Gaussian monocycle pulse (GMP) with the pulse width of 160 ps and single port eight throw (SP8T) switching matrices for controlling the combination of 4 × 4 cross-shaped dome antenna array. The detector is designed to be placed on the breast with the patient in the supine position. The detectability of malignant tumors is confirmed in excised breast tissues after total mastectomy surgery. The three-dimensional positions of the tumors in the imaging results are consistent with the results of histopathology analysis. The clinical tests are conducted by a clinical doctor for five patients at the hospital. The malignant tumors include invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). The final confocal imaging results are consistent with those of Magnetic Resonance Imaging (MRI), demonstrating the feasibility of the hand-held impulse-radar detector for malignant breast tumors.