National Cancer Center Hospital East Research Articles

A novel histopathological feature of spatial tumor-stroma distribution predicts lung squamous cell carcinoma prognosis.

We used a mathematical approach to investigate the quantitative spatial profile of cancer cells and stromain lung squamous cell carcinoma tissues and its clinical relevance. The study enrolled 132 patients with 3-5 cm peripheral lung squamous cell carcinoma, resected at the National Cancer Center Hospital East. We utilized machine learning to segment cancer cells and stroma on cytokeratin AE1/3 immunohistochemistry images. Subsequently, a spatial form of Shannon's entropy was employed to precisely quantify the spatial distribution of cancer cells and stroma. This quantification index was defined as the spatial tumor-stroma distribution index (STSDI). The patients were classified as STSDI-low and -high groups for clinicopathological comparison. The STSDI showed no significant association with baseline clinicopathological features, including sex, age, pathological stage, and lymphovascular invasion. However, the STSDI-low group had significantly shorter recurrence-free survival (5-years RFS: 49.5% vs. 76.2%, p < 0.001) and disease-specific survival (5-years DSS: 53.6% vs. 81.5%, p < 0.001) than the STSDI-high group. In contrast, the application of Shannon's entropy without spatial consideration showed no correlation with patient outcomes. Moreover, low STSDI was an independent unfavorable predictor of tumor recurrence and disease-specific death (RFS; HR = 2.668, p < 0.005; DSS; HR = 3.057, p < 0.005), alongside the pathological stage. Further analysis showed a correlation between low STSDI and destructive growth patterns of cancer cells within tumors, potentially explaining the aggressive nature of STSDI-low tumors. In this study, we presented a novel approach for histological analysis of cancer tissues that revealed the prognostic significance of spatial tumor-stroma distribution in lung squamous cell carcinoma.

336. EFFICACY AND SAFETY OF PHOTODYNAMIC THERAPY FOR SECONDARY PRIMARY ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER CHEMORADIOTHERAPY OR RADIOTHERAPY FOR ANOTHER MALIGNANCY

Abstract Background Photodynamic therapy (PDT) using talaporfin sodium is known as the effective, safe, and less invasive treatment for local failure after chemoradiotherapy (CRT) or radiotherapy (RT) for esophageal squamous cell carcinoma (ESCC). The secondary primary ESCC sometimes occur at different site after CRT/RT for ESCC or other cancer, and PDT may be considered for such lesion if endoscopic resection and surgery are not suitable for patients. However, the actual therapeutic efficacy remains unclear. This study aims to evaluate the efficacy and safety of PDT using talaporfin sodium for untreated secondary primary ESCC with a history of CRT/RT for another malignancy. Methods This retrospective study enrolled the patients underwent PDT using talaporfin sodium for untreated secondary primary ESCC in the treatment field of prior CRT/RT for another malignancy at the National Cancer Center Hospital East from September 2016 to October 2021. The inclusion criteria of PDT in this study were as follow; 1) invasion depth limited within T2, 2) &amp;lt;3/4 of the esophageal circumference, 3) absence of lymph node or distant metastasis, and 4) patient’s refusal or unsuitable physical condition for surgery. We evaluated the rate of local complete response (L-CR), incidence of adverse events, and clinical outcomes. Results Ten patients were enrolled in this study. Previous malignancy organ was hypopharynx (n=1), lung (n=2), and esophagus (n=7). All secondary primary ESCC were diagnosed as T1b. Finally, L-CR was achieved in 6 patients (L-CR rate: 60.0%). Among 6 patients with L-CR, one had local recurrence, one had lymph node recurrence, and the remaining four had no recurrence. During the median follow-up of 27.5 months, one patient with L-CR died from other diseases. Adverse events included grade ≤2 esophageal pain in 2 patients, photosensitivity and esophageal stricture in each one, and no esophageal perforation or treatment-related death. Conclusion As retreatment with RT is not available, PDT may be the treatment options for the secondary primary ESCC after CRT/RT for another malignancy.

Deciphering the prognostic value of FGFR2b/2c isoform expression levels in advanced esophagogastric cancer through whole-transcriptome sequencing.

53 Background: Fibroblast growth factor receptor (FGFR) isoform switching from FGFR2b to FGFR2c has been implicated in epithelial-to-mesenchymal transition and enhanced invasive potential in various malignancies and potentially be involved in resistance mechanisms to FGFR2b targeted therapy (e.g., bemarituzumab). This study sought to investigate the potential of respective FGFR2 isoform expression evaluation utilizing whole-transcriptome sequencing (WTS) and its correlation with therapeutic efficacy and clinical outcomes in patients with advanced G/GEJ cancer. Methods: Patients with advanced G/GEJ cancer who received systemic therapy at the National Cancer Center Hospital East between May 2021 and September 2023, and were enrolled in the immunological profiling study (UMIN000019129) and MONSTAR-SCREEN-2 (UMIN000043899) were included. FGFR2 protein and RNA expression were assessed via immunohistochemistry (IHC) and WTS with Caris MI Profile, respectively. FGFR2b and FGFR2c isoforms were distinguished by the detection of their respective splice junctions using WTS data. The FGFR2b/(2b+2c) ratio was stratified into FGFR2b-dominat and -containing subtypes using the median value. The log-rank test was used to discern differences in overall survival (OS). Results: Among the 129 patients, 21 (16.3%) exhibited FGFR2-positivity by IHC (staining intensity 2+ or 3+≥1% membranous staining of tumor cells), and a significant correlation was observed between FGFR2 IHC status and RNA expression levels (TPM: transcript per million) in WTS (FGFR2-positive, median TPM=11.1; FGFR2-negative, median TPM=4.7; P=0.002). The distribution of FGFR2b/(2b+2c) ratio (median, 0.89) was: 10.9% (0≤x&lt;0.2), 5.4% (0.2≤x&lt;0.4), 7.0% (0.4≤x&lt;0.6), 12.4% (0.6≤x&lt;0.8), 43.4% (0.8≤x&lt;1.0), and 20.9% (x=1.0). Among 58 patients treated with 1st line therapy, no significant difference in treatment response was observed between the FGFR2b-dominat (67.9%) and FGFR2c-containing subtypes (53.3%) (P=0.259). Overall, the FGFR2c-containing subtype was associated with significantly shorter OS compared to the FGFR2b-dominat subtype (median OS, 10.1 vs. 17.9 months; hazard ratio, 1.72; 95% confidence interval, 1.03-2.86; log-rank P=0.037). Conclusions: Our findings underscore the substantial concordance between IHC and WTS analysis of FGFR2, the feasibility of distinguishing FGFR2 isoforms using WTS, and the prognostic implications of FGFR2c isoform in patients with advanced G/GEJ cancer. Further analysis is warranted in patients receiving FGFR2b targeted treatment.

Efficacy of anti-PD-1 monotherapy for recurrent or metastatic olfactory neuroblastoma

BackgroundOlfactory neuroblastoma (ONB) is a rare malignant tumor of the head and neck. Due to its rarity, standard systemic therapy for this condition has yet to be established. In particular, the use of immune checkpoint inhibitors (ICIs) for the recurrent or metastatic (R/M) ONB population remains unclear.MethodsWe retrospectively evaluated 11 patients with R/M ONB who received any systemic chemotherapy at two Japanese institutions (National Cancer Center Hospital East and Kyushu Medical Center) between January 2002 and March 2022 and analyzed outcomes by use of anti-PD-1 antibody (nivolumab or pembrolizumab) monotherapy.ResultsOf the 11 patients, 6 received ICI (ICI-containing treatment group) and the remaining 5 were treated with systemic therapy but not including ICI (ICI-non-containing treatment group). Overall survival (OS) was significantly longer in the ICI-containing group (median OS: not reached vs. 6.4 months, log-rank p-value: 0.035). The fraction of ICI systemic therapy in the entire treatment period of this group reached 85.9%. Four patients (66.7%) in the ICI-containing treatment group experienced immune-related adverse events (irAE), with grades of 1/2. No irAE of grade 3 or more was seen, and no patient required interruption or discontinuation of treatment due to toxicity.ConclusionICI monotherapy appears to be effective and to contribute to prolonged survival in R/M ONB.

Robot-assisted transcervical esophagectomy with a bilateral cervical approach for thoracic esophagectomy.

Thoracic esophageal cancer resection through the neck approach has recently been reported as mediastinoscopic surgery. We present the first report of a new minimally invasive technique for thoracic esophageal cancer: robot-assisted transcervical esophagectomy with a bilateral cervical approach. Ten cases of robot-assisted bilateral transcervical esophagectomy performed at the National Cancer Center Hospital East, Japan, from February 2023 to August 2023 were reviewed. The short-term surgical outcomes were presented, and the feasibility and efficacy of this procedure were discussed. The mean operation time for the cervical procedure was 184.2 ± 23.6min. The total time for the whole procedure was 472.7 ± 28.4min, and total intraoperative blood loss was 162.2 ± 40.0ml. Among the 10 cases, one patient developed recurrent nerve paralysis, one patient developed pulmonary complications, and no patients developed postoperative pneumonia. The median postoperative hospital stay was 22 (range: 12-43) days. No patients developed severe postoperative surgical complications, which were graded as Clavien-Dindo ≥ III. The total number of surgically harvested mediastinal lymph nodes was 37.2 ± 11.2. Robot-assisted bilateral transcervical esophagectomy, a novel procedure for thoracic esophageal cancer, was safe and feasible. Using this procedure, the incidence of recurrent nerve palsy, which is a problem with transcervical esophagectomy and mediastinoscopic esophagectomy, is expected to decrease.

Safety and short-term efficacy of adjuvant nivolumab after neoadjuvant docetaxel, cisplatin, and fluorouracil for locally advanced esophageal squamous cell carcinoma.

271 Background: Efficacy and safety of adjuvant nivolumab has been demonstrated in patients with locally advanced esophageal cancer who received neoadjuvant chemoradiotherapy followed by surgery and had residual pathological disease in the CheckMate-577 trial. Although neoadjuvant docetaxel, cisplatin, and fluorouracil (DCF) is the standard neoadjuvant therapy for patients with locally advanced esophageal squamous cell carcinoma (ESCC) in Japan based on the JCOG1109 study, the safety and efficacy of adjuvant nivolumab in this population remains unclear. Here, we report the short-term safety and efficacy of adjuvant nivolumab after neoadjuvant DCF in patients with locally advanced ESCC. Methods: We retrospectively reviewed medical records of patients who received adjuvant nivolumab after neoadjuvant DCF and surgery for locally advanced ESCC from Nov 2021 to Jun 2023 at National Cancer Center Hospital East. Pathological stage was classified by UICC-TNM 8th edition. Adverse events were assessed according to CTCAE v5.0. Disease-free survival (DFS) was calculated by Kaplan-Meier method. Results: The study included a total of 33 patients with a median age of 67 years (range, 56-77), of which 29 patients were male. All patients had residual pathological disease, with ypStage I/II/III/IV of 5/1/16/11 patients. Median time from surgery to the initiation of adjuvant nivolumab was 10.6 weeks (range, 7.1-16.4 weeks). Treatment-related adverse events (TRAEs) occurred in 27 patients (82%), with pruritus (n = 13, 39%), rash (n = 7, 21%), hypothyroidism (n=7, 21%), xerosis (n = 6, 18%), diarrhea (n = 5, 15%), hypopituitarism (n = 5, 15%), pneumonitis (n = 1, 3%), and hepatic dysfunction (n = 1, 3%). Among these TRAEs, one patient developed grade 3 of hepatic dysfunction, which resolved with corticosteroid. TRAEs which led to discontinuation of nivolumab were hepatic dysfunction (n = 1, 3%), diarrhea (n = 1, 3%), and pneumonitis (n = 1, 3%). No treatment-related death was observed. With a median follow-up of 10.3 months, 1-year DFS rate was 63.3% (95% CI, 39.8-79.7%). Among 9 patients who experienced recurrence (locoregional; n = 3, distant; n = 6), 8 patients received subsequent therapy, including systemic chemotherapy (n = 5) and salvage chemoradiotherapy (n = 3). Conclusions: The safety and short-term efficacy of adjuvant nivolumab after neoadjuvant DCF and surgery was comparable to the results of the CheckMate-577 trial. Our study suggests that adjuvant nivolumab might be a possible treatment option in patients with locally advanced ESCC patients with residual pathological disease after neoadjuvant DCF followed by surgery.

Ten-year follow-up outcomes of limited resection trial for radiologically less-invasive lung cancer.

The JCOG0804/WJOG4507L single-arm confirmatory trial indicated a satisfactory 10-year prognosis for patients who underwent limited resection for radiologically less-invasive lung cancer. However, only one prospective trial has reported a 10-year prognosis. We conducted a multicenter prospective study coordinated by the National Cancer Center Hospital East and Kanagawa Cancer Center. We analyzed the long-term prognosis of 100 patients who underwent limited resection of a radiologically less-invasive lung cancer in the peripheral lung field. We defined radiologically less-invasive lung cancer as lung adenocarcinoma with a maximum tumor diameter of ≤2cm, tumor disappearance ratio of ≥0.5 and cN0. The primary endpoint was the 10-year local recurrence-free survival. Our patients, with a median age of 62years, included 39 males. A total of 58 patients were non-smokers; 87 had undergone wide wedge resection and 9 underwent segmentectomy. A total of four cases were converted to lobectomy because of the presence of poorly differentiated components in the frozen specimen or insufficient margin with segmentectomy. The median follow-up duration was 120.9months. The 10-year recurrence-free survival and overall survival rates of patients with lung cancer were both 96.0%. Following the 10-year long-term follow-up, two patients experienced recurrences at resection ends after wedge resection. Limited resection imparted a satisfactory prognosis for patients with radiologically less-invasive lung cancer, except two cases of local recurrence >5years after surgery. These findings suggest that patients with this condition who underwent limited resection may require continued follow-up >5years after surgery.

Prognosis of patients with residual pathological disease after neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy and surgery for esophageal squamous cell carcinoma: a retrospective cohort study.

Docetaxel, cisplatin, and 5-fluorouracil (DCF) combination chemotherapy has been established as one of the standard neoadjuvant therapies for locally advanced esophageal squamous cell carcinoma (ESCC). However, little is known about prognostic factors in patients with residual pathological disease after neoadjuvant DCF followed by surgery for locally advanced ESCC who are candidates for adjuvant nivolumab. This study aimed to investigate prognostic factors in patients with residual pathological disease after neoadjuvant DCF chemotherapy followed by surgery for locally advanced ESCC. This was a retrospective cohort study. This retrospective cohort study included patients who received neoadjuvant DCF followed by surgery for locally advanced ESCC between June 2014 and January 2020 at the National Cancer Center Hospital East. Among a total of 210 patients, 45 patients (21.4%) achieved a pathological complete response. The 3-year disease-free survival (DFS) rate was significantly lower in patients with residual pathological disease than in those with a pathological complete response [53.5% versus 74.5%; hazard ratio (HR): 2.09, 95% confidence interval (CI): 1.16-3.77, p = 0.01]. In patients with residual pathological disease (n = 165), multivariate analysis revealed that pathological node positivity (HR: 3.59, 95% CI: 1.92-6.71, p < 0.01), supraclavicular lymph node metastasis (HR: 2.15, 95% CI: 1.19-3.90, p = 0.01), and lymphovascular invasion (HR: 1.90, 95% CI: 1.14-3.17, p = 0.02) were significantly associated with poor DFS. In this largest-to-date cohort study, patients with residual pathological disease after neoadjuvant DCF followed by surgery for locally advanced ESCC had a poor prognosis. In these patients, pathological node positivity, including supraclavicular lymph node metastasis, and lymphovascular invasion were considered significant prognostic factors.

Potential Efficacy of Shiunko for Anti-Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody-Induced Skin Fissure: A Single Institutional Case Series.

Anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) is the key drug for RAS/BRAF V600E wild-type metastatic colorectal cancer (mCRC). However, anti-EGFR mAb-induced skin fissures often affect a patient's quality of life. Shiunko, a traditional Japanese topical herbal medicine, is used for burns and dermatitis and may potentially have wound-healing effects. Herein, we report cases of patients with mCRC who were treated with Shiunko for anti-EGFR mAb-induced skin fissure. We retrospectively reviewed consecutive patients with mCRC who received an anti-EGFR mAb-containing regimen and were treated with Shiunko twice a day for skin fissures at the National Cancer Center Hospital East between March 2022 and December 2022. Skin fissures were assessed at baseline and at every visit until 28 days after Shiunko initiation according to CTCAE v5.0. Among the 11 patients, 5 patients were female; the median age was 61 (range, 43-79) years. The median treatment duration with anti-EGFR mAb before Shiunko initiation was 13.1 (range, 6-52) weeks. Skin moisturizer and topical steroids were applied for skin fissures in 11 and 5 patients, respectively. All patients had grade 2 skin fissures at baseline of Shiunko initiation. Two weeks after Shiunko initiation, complete recovery was noted in 4 patients and improvement to grade 1 was noted in 6 patients. There were no Shiunko-related adverse events. Ten patients continued anti-EGFR mAb treatment until disease progression, while 1 patient discontinued anti-EGFR mAb treatment due to severe eruptions. Shiunko could be a treatment option for anti-EGFR mAb-induced skin fissure. Further studies are warranted to investigate the efficacy and safety of Shiunko for anti-EGFR mAb-induced skin fissure.

Weekly paclitaxel, carboplatin and cetuximab (PCE) combination followed by nivolumab for recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)

ObjectivesCetuximab-based chemotherapy is a standard 1st-line treatment for recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, few studies have reported survival data for a treatment sequence consisting of a PCE regimen (paclitaxel + carboplatin + cetuximab) followed by an immune checkpoint inhibitor. Materials and MethodsWe retrospectively assessed 37 patients with R/M SCCHN from the oral cavity, oropharynx, hypopharynx, and larynx who received PCE as 1st-line treatment followed by nivolumab as 2nd-line at the National Cancer Center Hospital East between December 2016 and July 2021. For comparison, we also analyzed 14 patients who did not receive nivolumab after PCE. ResultsOf the 37 patients who received nivolumab, overall response rate (ORR) by PCE was 48.6%, and median time to response and median progression-free survival (PFS) were 2.1 months (range: 0.8–4.8) and 4.4 months, respectively. In the nivolumab phase, ORR was 10.8%. 23 patients received 3rd-line therapy. Median PFS2, PFS3, and overall survival (OS) were 6.8, 11.6, and 19.5 months, respectively. Subgroup analysis by PD-L1 expression showed no significant difference in OS. Analysis of the comparison group revealed a trend toward improved OS in those who received nivolumab compared to those who did not (HR 0.47, 95%CI [0.19–1.13], p = 0.084). ConclusionPCE followed by nivolumab shows a favorable survival outcome, representing the potential for rapid tumor response with PCE and extension of OS by the addition of nivolumab regardless of combined positive score.

Safety of immune checkpoint inhibitors after proton beam therapy in head and neck mucosal melanoma: a case series.

Proton beam therapy (PBT) has shown promising efficacy in treating locally advanced head and neck mucosal melanoma despite its poor prognosis. Although PBT may improve the efficacy of subsequent immune checkpoint inhibitors (ICIs), the safety of ICIs in patients who have previously received PBT has not been established. Hence, this study evaluated the safety of ICIs in patients who had recurrent mucosal melanoma after PBT. Between April 2013 and June 2022, we retrospectively reviewed the medical records of patients diagnosed with cutaneous or mucosal melanoma at the National Cancer Center Hospital East. Seven patients were treated with ICIs after their head and neck mucosal melanoma (HNMM) recurred after PBT. Four of the seven patients experienced grade immune-related adverse events (irAEs). Due to irAE in the irradiation field, two patients had grade 3 hypopituitarism. Other grade 3 or higher irAEs included an increase in serum alanine aminotransferase in two patients and gastritis in one, and two patients discontinued ICI due to the irAEs. All irAEs were resolved with appropriate management. Although administering ICIs after PBT may increase the risk of irAEs, especially in the irradiation field, they appear manageable. These findings could help in the development of a treatment strategy for locally advanced HNMM that includes PBT and subsequent ICIs.

Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)

IntroductionIn locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and...

Eligibility for Photoimmunotherapy in Patients with Unresectable Advanced or Recurrent Head and Neck Cancer and Changes before and after Systemic Therapy.

Photoimmunotherapy is a novel cancer treatment that recently became covered by national health insurance in Japan, but treatment decision-making remains challenging for unresectable advanced or recurrent head and neck cancer. We aimed to clarify the characteristics of patients for whom photoimmunotherapy was indicated by a retrospective chart review. Patients aged ≥20 years diagnosed with advanced or recurrent head and neck cancer who started receiving systemic therapy at the National Cancer Center Hospital East from January 2016 through December 2020 were retrospectively analyzed. Before and after first-line systemic therapy, patients were classified into 3 groups according to eligibility for photoimmunotherapy: eligible, potentially eligible, and ineligible. In total, of 246 patients evaluated-194 after exclusions were analyzed-108 were deemed ineligible for treatment. Of the remaining 86 patients, 8 were considered potentially eligible and 9 eligible. Of the nine eligible patients, four became ineligible after receiving first-line systemic therapy due to disease progression. Our results suggest that the indication of photoimmunotherapy should be considered before, during, and after systemic therapy for unresectable locally advanced or recurrent head and neck cancer.

Hot snare polypectomy vs endoscopic mucosal resection using bipolar snare for intermediate size colorectal lesions: Propensity score matching.

Endoscopic resection (ER) with bipolar snare, in which the electric current only passes through the tissue between the device's two electrodes, is a prominent method used to prevent perforation due to electricity potentially. ER using bipolar snare with or without submucosal injection enabled safe resection of colorectal lesions measuring 10-15 mm in an ex vivo porcine model. ER with bipolar snare is expected to have good treatment outcomes in 10-15 mm colorectal lesions, with high safety even without submucosal injection. However, no clinical reports have compared treatment outcomes with and without submucosal injection. To compare the treatment outcomes of bipolar polypectomy with hot snare polypectomy (HSP) to those with endoscopic mucosal resection (EMR). In this single-centre retrospective study, we enrolled 10-15 mm nonpedunculated colorectal lesions (565 Lesions in 463 patients) diagnosed as type 2A based on the Japan Narrow-band Imaging Expert Team classification, resected by either HSP or EMR between January 2018 and June 2021 at the National Cancer Center Hospital East. Lesions were divided into HSP and EMR groups, and propensity score matching was performed. In the matched cohort, en bloc and R0 resection rates and adverse events were compared between the two groups. Of the 565 lesions in 463 patients, 117 lesions each in the HSP and EMR groups were selected after propensity score matching. In the original cohort, there was a significant difference in antithrombotic drug use (P < 0.05), lesion size (P < 0.01), location (P < 0.01), and macroscopic type (P < 0.05) between the HSP and EMR groups. In the matched cohort, the en bloc resection rates were comparable between both groups [93.2% (109/117) vs 92.3% (108/117), P = 0.81], and there was no significant difference in the R0 resection rate [77.8% (91/117) vs 80.3% (94/117), P = 0.64]. The incidence of delayed bleeding was similar in both groups [1.7% (2/117)]. Perforation occurred in the EMR group [0.9% (1/117)] but not in the HSP group. Using bipolar snare, ER of nonpedunculated 10-15 mm colorectal lesions may be performed safely and effectively, even without submucosal injection.

An accurate prediction of negative lymph node metastasis with consideration of glucose metabolism in early-stage non-small cell lung cancer.

We aimed to identify risk factors in lymph node metastasis in early-stage non-small cell lung cancer (NSCLC) and predict lymph node metastasis. A total of 416 patients with clinical stage IA2-3 NSCLC who underwent lobectomy and lymph node dissection between July 2016 and December 2020 at National Cancer Center Hospital East were included. Multivariable logistic regression was performed to develop a model for predicting lymph node metastasis. Leave-one-out cross-validation was performed to evaluate the developing prediction model, and sensitivity, specificity, and concordance statistics were calculated to evaluate its diagnostic performance. The formula for calculating the probability of pathological lymph node metastasis included SUVmax of the primary tumor and serum CEA level. The concordance statistics was 0.7452. When the cutoff value associated with the risk of incorrectly predicting pathological lymph node metastasis was 7.2%, the diagnostic sensitivity and specificity for predicting metastasis were 96.4% and 38.6%, respectively. We created a prediction model for lymph node metastasis in NSCLC by combining the SUVmax of the primary tumor and serum CEA levels, which showed a particularly strong association. This model is clinically useful as it successfully predicts negative lymph node metastasis in patients with clinical stage IA2-3 NSCLC.

Expression molecular subtype as a predictor of outcomes of chemoradiotherapy for esophageal cancer.

4030 Background: The standard treatment for advanced esophageal cancer is preoperative chemoradiotherapy (CRT) followed by surgery or definitive CRT (NCCN Guideline 2022 ver5). CRT has the advantage of preserving organs and functions and the prognosis for patients achieved complete response by CRT is good. However, it is currently impossible to predict the outcomes of CRT before treatment. We have performed RNA expression analysis of pre-treatment biopsy specimens of esophageal cancer and identified several intrinsic molecular subtypes, as well as E-type (high expression of squamous markers) with good prognosis for CRT and M2-type (high expression of stromal markers) with poor prognosis for CRT (US patent No 10,969,390 B2). Herein, we performed an integrated analysis to confirm the relationship between intrinsic expression molecular subtype classification and prognosis in the pooled population from two prospective cohort studies (UMIN000043637). Methods: Two cohort studies were as follows; 1) single institute prospective cohort study conducted at National Cancer Center Hospital East (n=157, UMIN-C000000459), 2) multicenter prospective cohort study conducted at 10 institutions (n=226, UMIN000016141). A total 383 cases met inclusion criteria and the Affymetrix U331Plus 2 panel (47,104 transcripts, 38,572 genes) was used to identify E-type and M2-type. The clinical course and outcome were blinded for subtype classification. Treatment was performed as usual at each institution, and treatment details and outcomes were examined by subtype. Results: Among 383 patients, 181 and 164 patients were treated by CRT and surgery, respectively. Ninety-nine percent (n=342) were squamous cell carcinoma. Stage I/II/III/IV were 13/61/86/21 and 17/63/81/3 in CRT group and surgery group, respectively. Among them, 76 (22%), 100 (29%), 169 (49%) patients were classified as E, M2 and others, respectively. Among the patients treated by CRT, CR rate of E-type and M2-type were 62.8% (95% CI, 47.8-75.7) and 33.3% (95% CI, 21.9-47.1) (p=0.006). The 5-year progression free survival (PFS) and overall survival (OS) rates of CRT group was 50.5% (95% CI, 34.7-64.4) and 59.8% (95% CI, 42.6-73.3) for E-type vs. 23.0% (95% CI, 12.0-36.2) and 29.0% (95%CI, 16.8-42.4) for M2-type, with statistically significant difference (p=0.011, p=0.003). Cox regression analysis showed that crude HR for PFS and OS of E vs M2 were 0.50 (95% CI, 0.296-0.859, p=0.012) and 0.41 (95% CI, 0.226-0750, p=0.004), respectively. In contrast, E and M2-type did not show the survival difference in surgery group. Conclusions: For the first time in the world, we confirmed that expression molecular subtype of esophageal cancer has the potential to predict the outcomes of CRT. The results may provide precision medicine in the selection of treatment for esophageal cancer.

A real-world assessment of the robustness of gel dosimetry

The purpose of this multi-institutional study was to evaluate the robustness of a transported gel dosimeter. Six vials were filled with a normoxic N-vinylpyrrolidone-based polymer gel dosimeter containing inorganic salt as a sensitizer (iVIPET), manufactured by Triangle Products (Kashiwa, Japan). Three vials were sent to the home institution (National Cancer Center Hospital East, Chiba, Japan) and three to an external institution. At each institution, vials received a dose of 0, 5, or 10 Gy using a 10 MV X-ray beam. After irradiation, the gel in the vial was imaged using a 3 T MRI scanner, and an R2 (spin–spin relaxation rate) map was created. The dose–R2 relationship was then analyzed using linear regression and the dose uncertainty computed. Thirty-four institutions participated in the study from July 2020 to July 2021. At the home institution, dose uncertainties were constant throughout the year (95% confidence interval [mean ± 1.96σ]: 3.3 ± 2.1% at 5 Gy and 4.0 ± 2.5% at 10 Gy). The ratio of the dose uncertainties measured at the external institutions and home institution was 1.1 ± 0.4 at 5 Gy (r = 0.88) and 1.0 ± 0.3 at 10 Gy (r = 0.81). Dose uncertainties were approximately 4% within 4 d of transportation but exceeded 10% when the gels were irradiated 7 d after fabrication. Temperature variations during transportation resulted in negligible uncertainties in absorbed dose; however, extended transportation times may increase dose uncertainty. Thus, polymer gel dosimeters should be used within 2–4 d of fabrication.

Preoperative steroid for enhancing patients’ recovery after head and neck cancer surgery with free tissue transfer reconstruction: protocol for a phase III, placebo-controlled, randomised, double-blind study (J-SUPPORT 2022, PreSte-HN Study)

IntroductionThere is no established methodology for the perioperative management of head and neck cancer surgery and free tissue transfer reconstruction (HNS-FTR). A single dose of corticosteroid administered immediately before surgery...

Advantages of robotic gastrectomy for overweight patients with gastric cancer: a comparison study of robotic gastrectomy and conventional laparoscopic gastrectomy.

A high body mass index (BMI) generally increases the risk of postoperative complications because of the intraperitoneal adipose tissue. Robotic gastrectomy (RG) decreases the surgical difficulty of conventional laparoscopic gastrectomy (LG) for these patients. We conducted the present study to identify the advantages of RG over LG for overweight patients. We reviewed clinical data on patients who underwent either LG or RG at the National Cancer Center Hospital East between January, 2014 and May, 2022. The 1298 patients eligible patients were divided into a non-overweight cohort (n = 996) (LG, n = 818; RG, n = 178) and an overweight cohort (n = 302) (LG, n = 250; RG, n = 52) according to a BMI cut-off of 25kg/m2. In the overweight cohort, the RG group had a lower incidence of grade ≥ III postoperative complications (0.0 vs. 8.8%, p = 0.01) and grade ≥ II postoperative complications (11.5 vs. 22.0%, p = 0.12) than the LG group. Multivariate analysis identified that RG was significantly associated with a lower incidence of grade ≥ II postoperative complications in the overweight cohort (odds ratio, 0.33; 95% confidence interval, 0.12-0.87; p = 0.02). RG may reduce the risk of postoperative complications, compared with conventional LG, in overweight patients.

The impact of the COVID-19 pandemic on perioperative chemotherapy for breast cancer.

Since it was first reported in December 2019, coronavirus disease 2019 (COVID-19) spread rapidly across the globe resulting in a pandemic. As of August 2022, seven outbreak peaks have been confirmed in Tokyo, and the numbers of new cases in the fifth and later outbreak periods have been far greater than in the preceding periods. This retrospective study examined the impact of the COVID-19 pandemic on perioperative chemotherapy for breast cancer. Patients with breast cancer who received perioperative chemotherapy at the National Cancer Center Hospital East were divided into 2 groups: 120 and 384 patients who started chemotherapy before and during the pandemic, respectively. The incidence of critical events that had potential detrimental effects on the prognosis, such as start of adjuvant chemotherapy ≥91 days after surgery and relative dose intensity of chemotherapy <85% were compared between groups. No significant difference in the incidence of critical events was found. When stratified by outbreak period, the incidence of critical events was positively correlated with the increasing number of new cases of COVID-19 (r = 0.83, p = 0.04). Moreover, 25/173 patients (14%) who started perioperative chemotherapy during the fifth and sixth outbreak periods developed COVID-19 infection, 80% of whom (20/25) had a delay or interruption to their surgery or other perioperative treatments. Although the impact of the COVID-19 pandemic on perioperative chemotherapy on whole groups of patients was not evident when comparing periods before and after the pandemic, the impact is becoming prominent in parallel with increasing numbers of new COVID-19 cases.