Risk stratification of oesophageal squamous cell carcinoma using change in total lesion glycolysis and number of PET-positive lymph nodes.

BACKGROUND: The efficacy of neoadjuvant chemotherapy (NACT) correlates with patient survival in oesophageal squamous cell carcinoma (OSCC), but optimal evaluation of the treatment response based on PET-CT parameters has not been established. METHODS: We analysed 226 OSCC patients who underwent PET-CT before and after NACT followed by surgery. We assessed SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for the primary tumour and the number of PET-positive lymph nodes before and after NACT to predict patient survival. RESULTS: In a stepwise analysis, we defined 60%, 80%, and 80% as the optimal cut-off values for SUVmax, MTV, and TLG reduction, respectively, to distinguish responders and non-responders to NACT. In the ROC analysis, the TLG reduction rate was the best predictor of recurrence among PET-CT parameters. The TLG responders achieved significantly more favourable prognoses than non-responders (2-year progression-free survival [PFS] rate: 64.1% vs. 38.5%; P = 0.0001). TLG reduction rate (HR 2.58; 95% CI 1.16-5.73) and the number of PET-positive lymph nodes after NACT (HR 1.79; 95% CI 1.04-3.08) were significant independent prognostic factors. CONCLUSIONS: TLG reduction is the best predictor of prognosis. Preoperative PET-CT evaluation of both the primary tumour and lymph nodes could accurately stratify risk in OSCC patients.

Immunoscore Signatures in Surgical Specimens and Tumor-Infiltrating Lymphocytes in Pretreatment Biopsy Predict Treatment Efficacy and Survival in Esophageal Cancer.

OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have long been recognized as playing an important role in tumor immune microenvironment. Lately, the Immunoscore (IS) has been proposed as a new method of quantifying the number of TILs in association with patient survival in several cancer types. METHODS: In 300 preoperatively untreated esophageal cancer (EC) patients who underwent curative resection at two different institutes, immunohistochemical staining using CD3 and CD8 antibodies was performed to evaluate IS, as objectively scored by auto-counted TILs in the tumor core and invasive margin. In addition, in pre-neoadjuvant chemotherapy (pre-NAC) endoscopic biopsies of a different cohort of 146 EC patients who received NAC, CD3, and CD8 were immunostained to evaluate TIL density. RESULTS: In all cases, the IS-high (score 3-4) group tended to have better survival [5-year overall survival (OS) of the IS-high vs low group: 77.6 vs 65.8%, P = 0.0722] than the IS-low (score 1-2) group. This trend was more remarkable in cStage II-IV patients (70.2 vs 54.5%, P = 0.0208) and multivariate analysis of OS further identified IS (hazard ratio 2.07, P = 0.0043) to be an independent prognostic variable. In preNAC biopsies, NAC-responders had higher densities than non-responders of both CD3 + ( P = 0.0106) and CD8 + cells ( P = 0.0729) and, particularly CD3 + cell density was found to be an independent prognostic factor (hazard ratio 1.75, P = 0.0169). CONCLUSIONS: The IS signature in surgical specimens and TIL density in preNAC- biopsies could be predictive markers of clinical outcomes in EC patients.

[A Case of Conversion Surgery after Nivolumab Monotherapy as Third-Line Therapy for Advanced Gastric Cancer].

A 79-year-old man with unresectable advanced gastric cancer due to invasion to the pancreas and positive lavage cytology( T4b, N+, M1, CY1, cStage ⅣB; Japanese classification of gastric carcinoma, 15th edition)received standard chemotherapy, including 6 courses of S-1 plus cisplatin as first-line therapy and 2 courses of paclitaxel plus ramucirumab followed by 6 courses of paclitaxel monotherapy as second-line therapy. The primary lesion became PD with these treatments. Subsequently, nivolumab monotherapy was introduced as third-line therapy. After 9 courses, the primary tumor shrunk, and lavage cytology turned to negative on diagnostic laparoscopy. We judged that the tumor was resectable, and the patient underwent radical total gastrectomy and D2 lymphadenectomy as conversion surgery. The pathological stage was ypT3(SS), N0, M0, CY0, and the therapeutic effect was Grade 1b. R0 resection was accomplished. He has been alive without recurrence for 18 months after resection without adjuvant chemotherapy.

[Tolerability and Outcome of Neoadjuvant GS Therapy for Resectable Pancreatic Cancer].

INTRODUCTION: Neoadjuvant chemotherapy with gemcitabine plus S-1(NAC GS)has been reported to prolong the prognosis of resectable pancreatic cancer, and is now being used in daily practice. In this study, we investigated the tolerability and outcome of neoadjuvant GS therapy for resectable pancreatic cancer in our hospital. PATIENTS: Fifty-two patients who underwent NAC GS for resectable pancreatic cancer between November 2019 and March 2023 were included in this study. RESULTS: The mean age of all 52 patients was 75 years, 28 were male and 24 were female. Tumor site was pancreatic head cancer in 32 patients, pancreatic body cancer in 13 patients, and pancreatic tail cancer in 8 patients. Only 2 patients of the 52 patients completed 2 cycles of GS therapy with full dose, and dose reduction and treatment deferral were performed in remaining 50 patients. The dose intensity was 78.4% for gemcitabine and 66.7% for S-1. Grade 3 or higher adverse events included neutropenia in 21 patients(40.4%), biliary tract infection in 6 patients(11.5%), fatigue, anorexia, hepatic dysfunction, and constipation in 1 patient each(1.9%). 47 patients(90.4%)underwent R0 resection. 4 patients had pancreatic fistula, which was classified as Grade Ⅲ by Clavien-Dindo, and one of them died in the hospital due to bleeding from a pseudoaneurysm. CONCLUSION: NAC GS therapy for resectable pancreatic cancer was considered feasible with appropriate management of adverse events.

Tumor-infiltrating M2 macrophage in pretreatment biopsy sample predicts response to chemotherapy and survival in esophageal cancer.

The association between the tumor microenvironment (TME) and treatment response or survival has been a recent focus in several types of cancer. However, most study materials are resected specimens that were completely modified by prior chemotherapy; therefore, the unmodified host immune condition has not yet been clarified. The aim of the present study was to evaluate the relationship between TME assessed in pre-therapeutic biopsy samples and chemoresistance in esophageal cancer (EC). A total of 86 endoscopic biopsy samples from EC patients who received neoadjuvant chemotherapy (NAC) prior to surgery were evaluated for the number of intratumoral CD4+ lymphocytes (with/without Foxp3 expression), CD8+ lymphocytes (with/without PD-1 expression), monocytes (CD14+ ) and macrophages (CD86+ , CD163+ and CD206+ ) by multiplex immunohistochemistry (IHC). The number of tumor-infiltrating CD206+ macrophages I significantly correlated with cT, cM, cStage and neutrophil/lymphocyte ratio (NLR), whereas the number of lymphocytes (including expression of Foxp3 and PD-1) was not associated with clinico-pathological features. The high infiltration of CD163+ or CD206+ macrophages was significantly associated with poor pathological response to NAC (P = 0.0057 and 0.0196, respectively). Expression of arginase-1 in CD163+ macrophages tended to be higher in non-responders (29.4% vs 18.2%, P = 0.17). In addition, patients with high infiltration of M2 macrophages exhibited unfavorable overall survival compared to those without high infiltration of M2 macrophages (5-year overall survival 57.2% vs 71.0%, P = 0.0498). Thus, a comprehensive analysis of TME using multiplex IHC revealed that M2 macrophage infiltration would be useful in predicting the response to NAC and long-term survival in EC patients.

[Multi-Look Staging Laparoscopy and Conversion Surgery for Gastric Cancer with Peritoneal Metastases].

A 46-year-old male patient with anorexia consulted our hospital. A scirrhous gastric cancer was found, and he was introduced to us. Laparoscopic examination was performed, and advanced peritoneal disseminated nodules were confirmed(CY1, P1). S-1 plus docetaxel therapy was introduced as first-line chemotherapy. Although the best effect judgment was PR, the primary lesion re-increased in size. We changed to the secondary weekly paclitaxel therapy. After 7 courses of the therapy, a second laparoscopic examination was performed, which confirmed the microscopic residual cancer cells(P1)in the reduced peritoneal nodules. Then, we performed 4 courses of intraperitoneal chemotherapy and a third laparoscopic examination. It showed CY0, P0, and we decided to perform conversion surgery. Total gastrectomy with D2 lymph node dissection was performed. The postoperative pathological diagnosis was ypT3N0M0, ypStageⅡA, and the histological effect judgment was Grade2 . S-1 oral administration was continued for 1 year as an adjuvant therapy, and recurrence was observed for 2 years.

[A Case of Inflammatory Breast Cancer with Very Severe Obesity].

A 39-year-old woman with very sever obesity was admitted to our hospital for a right breast redness and hardness. Her height, weight and BMI were 166 cm, 145 kg and 52.6 kg/m2. Her breast had peau d'orange. CT scan showed swelling of whole right breast and Level I , II lymph node. We performed core needle biopsy and diagnosed as the inflammatory breast cancer with ER and HER2 positive. We introduced chemotherapy(pertuzumab, trastuzumab and paclitaxel)and nutrition counseling in order to reduce her body weight. After 4 courses of chemotherapy, the clinical complete response was obtained and her body weight decreased to 125 kg. We performed mastectomy and axillary node resection and confirmed pathological complete response. Adjuvant chemotherapy(5-FU, epirubicin and cyclophosphamide), adjuvant trastuzumab therapy, postmastectomy radiation therapy and adjuvant hormonal therapy were administered. There have been no signs of recurrence as of 2 years after the operation.

[Locoregional recurrence of HER2-positive breast cancer - treatment after complete remission and long-term clinical benefits].

We report 7 cases of locoregional recurrence in human epidermal growth factor receptor 2 (HER2)-positive breast cancer that we treated. An early complete response (CR) and long-term response was achieved in 5 cases. There were 4 HER2- subtype and 3 Luminal HER2-type cases. Metastasis and recurrence were detected in the residual breast tissue and the supraclavicular, axillary, and parasternal lymph nodes. Chemotherapy consisting of trastuzumab was administered as first-line treatment. A CR was observed 3-4 months after the initiation of therapy in 4 cases, and the time to progression was 27.6- 65.8 months. After achieving a CR, 3 patients terminated treatment and 2 patients continued to take trastuzumab. However, due to adverse effects associated with the chemotherapy, 1 patient changed to endocrine therapy. A second, long-term, CR was achieved in 2 relapsed CR patients by re-challenging with the same chemotherapy regimen. Two patients did not achieve CR and died due to distant metastases. For a better quality of life, it is advisable to continue treatment after a clinical CR for solitary or more complex locoregional recurrences. Following the first-line therapy and a so-called chemoholiday, the patient's disease can be re-challenged using the previously sensitive regimen with careful observation.

[Two cases of radiotherapy-induced sarcoma after breast cancer surgery].

We report 2 cases of radiotherapy-induced sarcoma of the residual breast after breast cancer surgery. In 1 case, the patient was a 64-year-old woman. She underwent breast-conserving surgery and axillary lymph node dissection followed by irradiation to the residual breast in July 2001. A 1.1 × 1.0-cm tumor was noted in the residual breast 7 years 5 months after radiotherapy. An excisional biopsy was performed, and a histological diagnosis of angiosarcoma was made. She died of lung and peritoneal metastases 3 years 2 months after the diagnosis. In the other case, the patient was also 64 years old. She underwent breast-conserving surgery and sentinel lymph node biopsy followed by irradiation to the residual breast in October 2006. A 5.7 × 3.9-cm induration was noted in the residual breast 3 years 5 months after radiotherapy. A core needle biopsy was performed, and a histological diagnosis of sarcoma was made. Mastectomy was performed, and the histological diagnosis was malignant fibrous histiocytoma. She died of chest wall and intrapleural tumor recurrence 3 months after the mastectomy. Although radiotherapy-induced sarcoma is rare, early detection of the tumor in the irradiation area is important, as radiotherapy is often performed for breast cancer patients.

[The efficacy of early diagnosis of brain metastasis and systemic treatment after radiotherapy in patients with metastatic breast cancer].

We treated 9 patients diagnosed with brain metastasis from breast cancer. Although 1 patient was initially diagnosed as having Stage IV disease, 5 had Stage I/II early breast cancer. All patients had defined brain metastasis after chemotherapy. Brain metastasis was symptomatic in 7 patients, 4 of whom had brain edema, and asymptomatic in 2 patients. The median survival time from breast cancer metastasis was 23 days for patients who did not receive radiotherapy and 19.6 months for those who received radiotherapy. Among the patients treated with radiotherapy, the median survival time was 4.3 months for patients who did not receive further treatment and 19.7 months for those who received chemotherapy or chemotherapy with trastuzumab. One patient with a solitary brain metastasis underwent stereotactic radiosurgery, and treatment is being continued for 1 of the 2 patients who received systemic therapy after whole-brain radiotherapy and additional stereotactic radiosurgery at recurrence to control brain disease. Systemic treatment after radiotherapy is important for brain metastasis from breast cancer, and early diagnosis of brain metastasis facilitates the use of various available treatments.