Molecular subtypes of lung adenocarcinoma present distinct immune tumor microenvironments.

Overcoming resistance to immune checkpoint inhibitors is an important issue in patients with non-small-cell lung cancer (NSCLC). Transcriptome analysis shows that adenocarcinoma can be divided into three molecular subtypes: terminal respiratory unit (TRU), proximal proliferative (PP), and proximal inflammatory (PI), and squamous cell carcinoma (LUSQ) into four. However, the immunological characteristics of these subtypes are not fully understood. In this study, we investigated the immune landscape of NSCLC tissues in molecular subtypes using a multi-omics dataset, including tumor-infiltrating leukocytes (TILs) analyzed using flow cytometry, RNA sequences, whole exome sequences, metabolomic analysis, and clinicopathologic findings. In the PI subtype, the number of TILs increased and the immune response in the tumor microenvironment (TME) was activated, as indicated by high levels of tertiary lymphoid structures, and high cytotoxic marker levels. Patient prognosis was worse in the PP subtype than in other adenocarcinoma subtypes. Glucose transporter 1 (GLUT1) expression levels were upregulated and lactate accumulated in the TME of the PP subtype. This could lead to the formation of an immunosuppressive TME, including the inactivation of antigen-presenting cells. The TRU subtype had low biological malignancy and "cold" tumor-immune phenotypes. Squamous cell carcinoma (LUSQ) did not show distinct immunological characteristics in its respective subtypes. Elucidation of the immune characteristics of molecular subtypes could lead to the development of personalized immune therapy for lung cancer. Immune checkpoint inhibitors could be an effective treatment for the PI subtype. Glycolysis is a potential target for converting an immunosuppressive TME into an antitumorigenic TME in the PP subtype.

Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306.

BACKGROUND: In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis. METHODS: We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined. RESULTS: ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175-0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073-0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is. CONCLUSIONS: RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0.

Lung Oligometastasis of Breast Cancer: Prospective Cohort Study of Treatment Strategies (SBP-06).

While local treatment of metastases is considered to be unrelated to prognosis, previous studies have suggested that local treatment of isolated lung metastases may have positive prognostic impact. We designed this prospective cohort study to investigate the clinical situation and its outcomes. We enrolled patients with fewer than 3 lung nodules suspected of being oligometastases after curative breast cancer surgery. Treatments, including local and systemic therapy, were selected by the physician and patient in consultation. The primary outcome was overall survival (OS); secondary outcomes were the efficacy and the safety of the surgery for lung oligometastases. Between May 2015 and May 2019, 14 patients were enrolled. Resection of lung nodules (metastasectomy) was performed in 11 (78.6%) of 14 patients, and one of these cases was diagnosed as primary lung cancer. Metastasectomies were all performed employing video-assisted thoracic surgery (VATS) without perioperative complications. Systemic therapies were administered to all patients except one. The respective 3-year and 5-year OS rates of patients with lung oligometastases were 91.6% and 81.5%, respectively. Progression occurred in 6 patients: 3 of the 10 with metastasectomy and all 3 without this surgical procedure. Lung metastasectomy was worthwhile as a diagnostic evaluation and may provide long-term benefit in some patients.

Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer.

PURPOSE: Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain. METHODS: We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided. RESULTS: Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39-0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33). CONCLUSIONS: The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease.

Authorship by gender in anesthesiology journals: a retrospective cross-sectional study for Japan.

PURPOSE: Although it is important to recognize gender disparities in publishing to achieve gender diversity, women's authorship in Japan remains unclear. Therefore, this study aimed to investigate the percentage and analyze the trends of articles authored and published in anesthesiology journals by Japanese female authors. METHODS: The genders of the first and last authors affiliated with Japanese institutions were surveyed in the Journal of Anesthesia (JA) (1990, 1995, and 2000-2022) and 11 international anesthesiology journals (2010-2022). RESULTS: We included 845 and 819 original research articles from JA in the analyses of the first and last authors, respectively. The proportion of female first authors significantly increased from 41 (11.7%) out of 351 before 2009 to 119 (24.1%) out of 494 after 2010 (p < 0.001). The proportion of female last authors was 11 (3.3%) out of 335 before 2009 and 22 (4.5%) out of 484 after 2010, respectively, with no significant difference (p = 0.470). We included 624 and 572 original research articles from international anesthesiology journals in the analyses of first and last authors, respectively. Among these, there were 134 (21.5%) and 23 (4.0%) female first and last authors, respectively. These proportions in international anesthesiology journals did not significantly differ from those in JA (p = 0.334, p = 0.789, respectively). CONCLUSION: The percentage of female first authors has increased, commensurate with the percentage of female anesthesiologists. However, the percentage of female last authors has not increased and remains low in Japan.

A prediction model for early systemic recurrence in breast cancer using a molecular diagnostic analysis of sentinel lymph nodes: A large-scale, multicenter cohort study.

BACKGROUND: The one-step nucleic acid amplification (OSNA) assay can quantify the cytokeratin 19 messenger RNA copy number as a proxy for sentinel lymph node (SN) metastasis in breast cancer. A large-scale, multicenter cohort study was performed to determine the prognostic value of the SN tumor burden based on a molecular readout and to establish a model for the prediction of early systemic recurrence in patients using the OSNA assay. METHODS: SN biopsies from 4757 patients with breast cancer were analyzed with the OSNA assay. The patients were randomly assigned to the training or validation cohort at a ratio of 2:1. On the basis of the training cohort, the threshold SN tumor burden value for stratifying distant recurrence was determined with Youden's index; predictors of distant recurrence were investigated via multivariable analyses. Based on the selected predictors, a model for estimating 5-year distant recurrence-free survival was constructed, and predictive performance was measured with the validation cohort. RESULTS: The prognostic cutoff value for the SN tumor burden was 1100 copies/µL. The following variables were significantly associated with distant recurrence and were used to construct the prediction model: SN tumor burden, age, pT classification, grade, progesterone receptor, adjuvant cytotoxic chemotherapy, and adjuvant anti-human epidermal growth factor receptor 2 therapy. The values for the area under the curve, sensitivity, specificity, and accuracy of the prediction model were 0.83, 63.4%, 81.7%, and 81.1%, respectively. CONCLUSIONS: Using the OSNA assay, the molecular readout-based SN tumor burden is an independent prognostic factor for early breast cancer. This model accurately predicts early systemic recurrence and may facilitate decision-making related to treatment.

Pathological Complete Response Patients after Neoadjuvant Chemotherapy in Breast Cancer.

Cases of breast cancer metastasis after achieving a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) are sometimes encountered in clinical practice. We investigated the prognostic factors for pCR in patients with breast cancer after NAC. This retrospective cohort study included patients with localized breast cancer who underwent NAC followed by surgery between 2004 and 2020 and achieved a pCR. The associations between clinical factors and distant metastasis-free survival rate were statistically analyzed. We analyzed data for 127 patients. Twelve patients (9.4%) had distant metastases, and seven (5.5%) died. For estrogen receptor (ER)-positive patients, the distant metastasis-free survival rate was 94.6% for both 5 and 8 years. In contrast, ER-negative patients had a distant metastasis-free survival rate of 87.6% and 85.4% for 5 and 8 years (p=0.094), respectively. In cT0-2 patients, the distant metastasis-free survival rate was 92.4% for 5 years and 90.5% for 8 years, whereas in cT3-4 patients, the distant metastasis-free survival rate was 83.5% for 5 years and 83.5% for 8 years (p=0.301). This study suggested that patients with ER-negative, pre-NAC cT3 or T4 breast cancer who had achieved a pCR after NAC tended to have a worse prognosis.

[A Multicenter Retrospective Study of Predictors of Duration of Treatment with Palbociclib].

Palbociclib(PAL), which is a small molecule with inhibitory activity against cyclin-dependent kinase 4/6, is used in endocrine combined therapy for the treatment of estrogen receptor(ER)-positive and HER2-negative inoperable and recurrent breast cancer. We retrospectively investigated the factors associated with prolonged treatment in inoperable and recurrent breast cancer in a multicenter study. The median time-to-treatment failure(TTF)after PAL was 5.6 months(0.2-22.5). A total of 28 patients in the fulvestrant(FUL)group and 21 patients in the aromatase inhibitor(AI)group received concomitant endocrine therapy. The median TTF was 2.6 vs 6.7 months(p=0.015)for white blood cell(WBC), 3.7 vs 6.6 months (p=0.021)for neutrophils(Neu), and 2.8 vs 7.5 months(p=0.007)for lymphocytes(Lym). The treatment period tended to be prolonged in the group with higher WBC, Neu, and Lym levels than that of the standard values. The median treatment duration of the FUL group was 7.5 months vs 4.2 months(p=0.162); however, the difference was not statistically significant. The WBC, Neu, and Lym levels upon PAL introduction may be factors affecting the prolonged treatment. Further analysis of the data and further investigation of the prolongation-related factors of PAL treatment period are necessary.

Multicenter retrospective study on the use of Curebest™ 95GC Breast for estrogen receptor-positive and node-negative early breast cancer.

BACKGROUND: The benefits of postoperative chemotherapy in patients with estrogen receptor (ER)-positive breast cancer remain unclear. The use of tumor grade, Ki-67, or ER expression failed to provide an accurate prognosis of the risk of relapse after surgery in patients. This study aimed to evaluate whether a multigene assay Curebest™ 95GC Breast (95GC) can identify the risk of recurrence and provide more insights into the requirements for chemotherapy in patients. METHODS: This single-arm retrospective multicenter joint study included patients with ER-positive, node-negative breast cancer who were treated at five facilities in Japan and had received endocrine therapy alone as adjuvant therapy. The primary lesion specimens obtained during surgery were analyzed using the 95GC breast cancer multigene assay. Based on the 95GC results, patients were classified into low-risk (95GC-L) and high-risk (95GC-H) groups. RESULTS: The 10-year relapse-free survival rates were 88.4 and 59.6% for the 95GC-L and 95GC-H groups, respectively. Histologic grade, Ki-67, and PAM50 exhibited a significant relationship with the 95GC results. The segregation into 95GC-L and 95GC-H groups within established clinical factors can identify subgroups of patients using histologic grade or PAM50 classification with good prognosis without receiving chemotherapy. CONCLUSIONS: Based on the results of our retrospective study, 95GC could be used to evaluate the long-term prognosis of ER-positive, node-negative breast cancer. Even though further prospective validation is necessary, the inclusion of 95GC in clinical practice could help to select optimal treatments for breast cancer patients and identify those who do not benefit from the addition of chemotherapy, thus avoiding unnecessary treatment.

Prospective study of hair recovery after (neo)adjuvant chemotherapy with scalp cooling in Japanese breast cancer patients.

PURPOSE: Scalp cooling during chemotherapy infusion to mitigate alopecia for breast cancer patients is becoming widespread; however, studies regarding hair recovery after chemotherapy with scalp cooling are limited. We conducted a prospective study of hair recovery after chemotherapy with scalp cooling. PATIENTS AND METHODS: One hundred and seventeen Japanese female breast cancer patients who completed planned (neo)adjuvant chemotherapy using the Paxman Scalp Cooling System for alopecia prevention were evaluated for alopecia prevention in our prospective study. We evaluated their hair recovery 1, 4, 7, 10, and 13 months after chemotherapy. Primary outcomes were grades of alopecia judged by two investigators (objective grades) and patients' answers to the questionnaire regarding the use of a wig or hat (subjective grades). RESULTS: Of 117 patients, 75 completed scalp cooling during the planned chemotherapy cycles (Group A), but 42 discontinued it mostly after the first cycle (Group B). Objective and subjective grades were significantly better in Group A than in Group B throughout 1 year, and at 4 and 7 months after chemotherapy. When we restricted patients to those with objective Grade 3 (hair loss of > 50%) at 1 month, Group A exhibited slightly faster hair recovery based on the objective grades than Group B. There was less persistent alopecia in Group A than in Group B. CONCLUSIONS: Scalp cooling during chemotherapy infusion for Japanese breast cancer patients increased the rate of hair recovery and had preventive effects against persistent alopecia.

Scalp cooling for hair loss prevention in female Japanese breast cancer patients receiving (neo)adjuvant chemotherapy.

PURPOSE: Scalp cooling during chemotherapy infusion has been recently reported to have moderate efficacy in the mitigation of chemotherapy-induced alopecia; however, there are few reports on Asian patients. We aimed to clarify the effects of scalp cooling in Japanese women. PATIENTS AND METHODS: Female Japanese breast cancer patients who planned to receive (neo)adjuvant chemotherapy participated in this prospective study on the efficacy of scalp cooling using the Paxman Scalp Cooling System for alopecia prevention. The primary outcomes were the rates of patients with Grade 3 alopecia (defined as hair loss of > 50%) and the rates of patients who used a wig or hat to conceal hair loss 1 month after the last infusion of chemotherapy. The subjects were given a brief questionnaire regarding headaches, bad mood, fatigue, and chills shortly after each cooling. RESULTS: One hundred and forty-three patients participated in the study and used the cooling cap at least once. The mean and median ages of the subjects were 50.6 and 50, respectively (age range 28-76). One hundred and twenty-nine patients completed the planned chemotherapy of 4 to 8 cycles. Among them (7 patients were not evaluable), 74 patients (60.7%) had Grade 3 alopecia 1 month after chemotherapy. Of 80 patients who used the scalp cooling system throughout the planned chemotherapy (1 patient was not evaluable), 36 patients (45.6%) experienced Grade 3 alopecia. CONCLUSION: The efficacy of scalp cooling during chemotherapy infusion for hair loss mitigation in Asian women is similar to that in Caucasian women.

Optimizing the timing of 3.6 mg Pegfilgrastim Administration for Dose-Dense Chemotherapy in Japanese Patients with Breast Cancer.

Perioperative dose-dense chemotherapy (DDCT) with pegfilgrastim (Peg) prophylaxis is a standard treatment for high-risk breast cancer. We explored the optimal timing of administration of 3.6 mg Peg, the dose approved in Japan. In the phase II feasibility study of DDCT (adriamycin+cyclophosphamide or epirubicin+cyclophosphamide followed by paclitaxel) for breast cancer, we investigated the feasibility, safety, neutrophil transition, and optimal timing of Peg treatment by administering Peg at days 2, 3, and 4 post-chemotherapy (P2, P3, and P4 groups, respectively). Among the 52 women enrolled, 13 were aged > 60 years. The anthracycline sequence was administered to P2 (n=33), P3 (n=5), and P4 (n=14) patients, and the taxane sequence to P2 (n=38) and P3 (n=6) patients. Both sequences showed no interaction between Peg administration timing and treatment discontinuation, treatment delay, or dose reduction. However, the relative dose intensity (RDI) was significantly different among the groups. The neutrophil count transition differed significantly among the groups receiving the anthracycline sequence. However, the neutrophil count remained in the appropriate range for both sequences in the P2 group. The timing of Peg administration did not substantially affect the feasibility or safety of DDCT. Postoperative day 2 might be the optimal timing for DDCT.

[Clinical experience with gemcitabine treatment for metastatic breast cancer].

It is difficult to cure recurrent or metastatic breast cancer (MBC). Therefore, it is important to continue treatment for MBC with maintenance of quality of life (QOL). Gemcitabine has been approved for MBC since February 2010. We administered gemcitabine to 39 patients with MBC between February 1, 2010 and March 31, 2012. Depending on the case, taxane or trastuzumab was added. Almost all patients had received prior chemotherapy or hormonal therapy. The median age of patients was 61 years (range, 33-82 years), and the median number of previous treatment regimens was 3 (range, 0-6). The response rate was 15.4%, the disease control rate was 56.4%, and the clinical benefit rate was 33.3%. The main hematological adverse event was neutropenia, and the main non-hematological adverse event was fatigue. Neutropenia could be managed by reducing the gemcitabine dose or withdrawing treatment. Adverse events requiring hospitalization were not observed. These findings suggest that gemcitabine-based regimens are feasible in terms of efficacy and maintenance of QOL for patients with MBC.

[Genetic counseling and practice of hereditary cancers at Shikoku Cancer Center].

Although the progress in understanding human genetics regarding cancer has been applied to the medical practice of treating hereditary cancers in developed western countries, it is not widely implemented in Japan. We started treating hereditary cancers at NHO Shikoku Cancer Center in November 2000. Our institution has a multidisciplinary team that provides medical care and genetic counseling for patients with hereditary cancers, and their relatives. The team consists of doctors from several related departments, and paramedics including a genetic counselor who participated as of 2009. Medical care of patients with hereditary cancers should not be separated from general oncological practice, but incorporate all medical professionals, including doctors of related departments and paramedic. We have attempted to identify patients with hereditary cancer and their family members and relatives at high risk; we followed them up and provided risk-reducing therapies for them at our cancer center. Here we present the framework of our practice in treating hereditary cancers. We discuss appropriate goals and future perspectives in the field of hereditary cancer in Japan.

Pembrolizumab-Associated Pneumonitis Resembling Lymphangitic Carcinomatosis in a Melanoma Patient.

ABSTRACT: In recent years, many articles have described the adverse events associated with immune checkpoint inhibitors. We report the case of a 63-year-old woman with bilateral lung shadows after 1-year pembrolizumab immunotherapy following surgery for the right-foot melanoma because of positive sentinel lymph nodes. Follow-up 18 F-FDG PET/CT demonstrated bilateral diffuse mass-like peribronchovascular opacities with marked FDG uptake. Clinically, melanoma metastases with lymphangitic spread were suspected, and bronchoscopy was performed, although no evidence of malignancy was found. The lung shadow was mostly resolved after steroid treatment. Pembrolizumab-induced pneumonitis can be a mimicker of melanoma metastasis with lymphangitic spread.

Patients Offer Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (PO-RAFAELO) Study under the Patient-proposed Health Services.

Introduction: Due to the increase in the number of early-stage breast cancer patients, there is growing interest in minimally invasive local therapies for breast cancer. Radiofrequency ablation (RFA) therapy is one of the most promising minimally invasive treatments. The Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (RAFAELO) study, a multicenter collaborative study that aims to validate the efficacy and safety of RFA and to standardize its use for early-stage breast cancer, was conducted under the Advanced Medical Care B system in 2013. This study enrolled the expected number of patients in November 2017; moreover, it is currently in the follow-up period. Some patients with early-stage breast cancer who are eligible for RFA could not receive the RFA treatment, as it is still not covered by insurance. Therefore, the Patients Offer Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (PO-RAFAELO) study under the Patient-proposed Health Services (PPHS) was proposed and approved in March 2019. Methods: The PPHS is a system that allows patients to receive prompt access to advanced medical care at a medical facility close to them, starting with their request. This system is considered a part of the specific and special medical coverage. The PO-RAFAELO study is the only study in the surgical field utilizing the PPHS, aiming to help in achieving regulatory approval and insurance coverage of RFA for breast cancer. Results: As of January 2023, 120 patients have undergone RFA using the PPHS and no grade 3 or higher early adverse events have occurred. Conclusions: A certain number of patients with early-stage breast cancer prefer nonsurgical treatment, and it is important to provide information regarding the availability of RFA for early-stage breast cancer under the PPHS.Trial registration: registered with Japan Registry of Clinical Trial on March 06, 2019 (Trial ID: jRCTs032180187).

Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations.

Resistance to immune checkpoint blockade remains challenging in patients with non-small cell lung cancer (NSCLC). Tumor-infiltrating leukocyte (TIL) quantity, composition, and activation status profoundly influence responsiveness to cancer immunotherapy. This study examined the immune landscape in the NSCLC tumor microenvironment by analyzing TIL profiles of 281 fresh resected NSCLC tissues. Unsupervised clustering based on numbers and percentages of 30 TIL types classified adenocarcinoma (LUAD) and squamous cell carcinoma (LUSQ) into the cold, myeloid cell-dominant, and CD8+ T cell-dominant subtypes. These were significantly correlated with patient prognosis; the myeloid cell subtype had worse outcomes than the others. Integrated genomic and transcriptomic analyses, including RNA sequencing, whole-exome sequencing, T-cell receptor repertoire, and metabolomics of tumor tissue, revealed that immune reaction-related signaling pathways were inactivated, while the glycolysis and K-ras signaling pathways activated in LUAD and LUSQ myeloid cell subtypes. Cases with ALK and ROS1 fusion genes were enriched in the LUAD myeloid subtype, and the frequency of TERT copy-number variations was higher in LUSQ myeloid subtype than in the others. These classifications of NSCLC based on TIL status may be useful for developing personalized immune therapies for NSCLC. Significance: The precise TIL profiling classified NSCLC into novel three immune subtypes that correlates with patient outcome, identifying subtype-specific molecular pathways and genomic alterations that should play important roles in constructing subtype-specific immune tumor microenvironments. These classifications of NSCLC based on TIL status are useful for developing personalized immune therapies for NSCLC.

Detection of isolated ipsilateral regional lymph node recurrences by F18-fluorodeoxyglucose positron emission tomography-CT in follow-up of postoperative breast cancer patients.

Imaging diagnostic methods except for mammograms are not recommended for follow-up of postoperative breast cancer patients in order to detect small recurrences because of the poor survival improvement in earlier randomized trials. However, the use of new imaging modalities may improve survival by detection of small isolated regional lymph node recurrences which are potentially curable. Between April 2006 and December 2008, we used PET-CT to find small recurrences in follow-up of 1,907 postoperative breast cancer patients. A total of 3,280 PET-CT imagings were performed. The median age at PET-CT imaging was 58 years, with a median 48-month interval from definitive surgery to the PET-CT imaging. Twenty-two patients were found to have isolated ipsilateral regional recurrences only by PET-CT (axillary node recurrences in 6, infraclavicular node recurrences in 5, supraclavicular node recurrences in 6, and parasternal node recurrences in 5). All of those recurrences were missed by palpation or were nonpalpable. The pathological lymph node status at the definitive surgery for the primary breast cancer of 22 patients with the isolated ipsilateral regional lymph node recurrences was positive in 17 patients. If patients are limited to those who had pathologically positive node(s) at definitive surgery, the incidence of patients with isolated regional lymph node recurrences found only by PET-CT would be 2.6% (17/663 patients). Seventeen other asymptomatic cancers including contralateral breast cancers were found only by PET-CT. Early detection of isolated loco-regional recurrences of breast cancer is suggested to result in improved survival. Therefore, the use of PET-CT in follow-up of postoperative node-positive breast cancer patients may improve their survival because of early detection of isolated regional lymph node recurrences which are still potentially curable, and screening of other asymptomatic cancers.

[Efficacy and safety of aprepitant in patients with breast cancer].

We retrospectively analyzed the efficacy and safety of aprepitant in breast cancer patients who were treated with FEC(5- fluorouracil, epirubicin, cyclophosphamide)or EC(epirubicin, cyclophosphamide). We divided patients into two groups according to the aprepitant approval period. The rate of severe nausea(@Grade 2)was significantly less in patients with aprepitant(acute 10. 0%, delayed 15. 0%)than those without aprepitant(acute 29. 1%, delayed 30. 9%). Complete response( no vomiting and no use of rescue therapy)in the acute phase was significantly higher in the aprepitant pretreated group than in the no aprepitant group(82. 5% vs 61. 8%, respectively). Moreover, complete response in the delayed phase was also higher in the aprepitant group than in the no aprepitant group(82. 5%vs 58. 2%, respectively). Pre-treatment with aprepitant did not increase adverse events including constipation and elevation of alanine transaminase. The aprepitant was effective in terms of prevention of chemotherapy-induced nausea and vomiting in patients treated with an anthracycline- based regimen.

A Case of Multiple Liver Metastases after Surgery in Elderly HER2-Positive Breast Cancer in Which Anastrozole + Trastuzumab Was Ineffective but T-DM1 Was Effective.

Chemotherapy is often difficult to treat human epidermal growth factor receptor 2 (HER2)-positive metastatic recurrent breast cancer in the elderly, and no standard treatment has been established at this point. We experienced a case in which trastuzumab (Tmab) + anastrozole (ANA) was ineffective (progressive disease; PD) in elderly HER2-positive breast cancer with postoperative multiple liver metastases, but T-DM1 was significantly effective (complete response; CR), and treatment could be continued safely. An 82-year-old woman was referred to our department with a right breast mass. A close examination revealed right breast cancer cT1bN0M0 cStage I, and total mastectomy and sentinel lymph node biopsy were performed. The postoperative pathological result was pT1bN0M0 pStage I (luminal HER2 type). The patient was elderly and had no adjuvant treatment after the operation. Approximately 2 years after the operation, multiple liver metastases were observed, and treatment with ANA and Tmab was started. Four months later, MRI showed that the number of multiple liver metastases increased. The patient was diagnosed with PD, and the anti-HER2 drug was changed from trastuzumab to trastuzumab emtansine (T-DM1). The dose was reduced due to vomiting (grade 3). Two months later, MRI showed that the multiple liver metastases shrank and became obscure after 5 months. After that, T-DM1 was continued, and the disease did not worsen. In elderly people with difficulty in administering chemotherapy, T-DM1 may have a safe and sufficient therapeutic effect by adjusting the dose and managing side effects appropriately.