Japanese Foundation For Cancer Research Research Articles

Clinical utility of the carcinoembryonic antigen level in patients with stage III colon cancer after surgery and adjuvant chemotherapy.

The association between perioperative and post-adjuvant carcinoembryonic antigen (CEA) levels and recurrence and prognosis remains unclear. We aimed to evaluate whether perioperative CEA levels are an integral component of the assessment of recurrence and prognosis of patients with stage III colon cancer (CC). This retrospective study was conducted at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 2005 to 2013. We enrolled patients with stage III CC who underwent complete resection of a primary tumor and received adjuvant chemotherapy. We analyzed the association between perioperative and post-adjuvant CEA levels and recurrence-free survival (RFS) and overall survival (OS). A total of 564 consecutive patients were included in the analysis. The RFS and OS of patients with high postoperative CEA levels were significantly worse than those of patients with normal postoperative CEA levels. In the multivariate analysis, high postoperative CEA levels were associated with shorter RFS and OS. The number of risk factors, postoperative CEA levels, and T/N-stage all had a cumulative effect on RFS and OS. High postoperative CEA levels and the number of risk factors are associated with recurrence and worse prognosis for patients with stage III CC.

Dosiomics for intensity-modulated radiotherapy in patients with prostate cancer: survival analysis stratified by baseline prostate-specific antigen and Gleason grade group in a 2-institutional retrospective study.

This study evaluated the prognostic impact of the quality of dose distribution using dosiomics in patients with prostate cancer, stratified by pretreatment prostate-specific antigen (PSA) levels and Gleason grade (GG) group. A total of 721 patients (Japanese Foundation for Cancer Research [JFCR] cohort: N = 489 and Tokyo Radiation Oncology Clinic [TROC] cohort: N = 232) with localized prostate cancer treated by intensity-modulated radiation therapy were enrolled. Two predictive dosiomic features for biochemical recurrence (BCR) were selected and patients were divided into certain groups stratified by pretreatment PSA levels and GG. Freedom from biochemical failure (FFBF) was estimated using the Kaplan-Meier method based on each dosiomic feature and univariate discrimination was evaluated using the log-rank test. As an exploratory analysis, a dosiomics hazard (DH) score was developed and its prognostic power for BCR was examined. The dosiomic feature extracted from planning target volume (PTV) significantly distinguished the high- and low-risk groups in patients with PSA levels >10 ng/mL (7-year FFBF: 86.7% vs 76.1%, P < .01), GG 4 (92.2% vs 76.9%, P < .01), and GG 5 (83.1% vs 77.8%, P = .04). The DH score showed significant association with BCR (hazard score: 2.04; 95% confidence interval: 1.38-3.01; P < .001). The quality of planned dose distribution on PTV may affect the prognosis of patients with poor prognostic factors, such as PSA levels >10 ng/mL and higher GGs. The effects of planned dose distribution on prognosis differ depending on the patient's clinical background.

Evaluation of the Leftover Capecitabine Tablets in Adjuvant CAPOX Chemotherapy for Gastric Cancer

Since it is important that patients take their oral anticancer therapy as prescribed, pharmacists need to assess adherence. In addition, oral anticancer drugs are expensive, and reuse of leftover drugs at outpatient pharmacy clinics is useful in reducing drug costs. The present study aimed to clarify when and why patients have leftover capecitabine tablets, and the cost of leftover capecitabine tablets reused at an outpatient pharmacy clinic, focusing on adjuvant capecitabine plus oxaliplatin (CAPOX) chemotherapy for gastric cancer. We retrospectively studied patients who received adjuvant CAPOX chemotherapy for gastric cancer between November 1, 2015, and April 30, 2021, at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The cost of leftover capecitabine reused by pharmacists was calculated based on the National Health Insurance drug price standard for the study period. This study included 64 patients who received adjuvant CAPOX chemotherapy. Thirty-seven patients had 152 leftover capecitabine tablets. The most common reasons for leftover capecitabine tablets were nausea and vomiting (21.7%), missed doses (18.4%), and diarrhea (13.2%). The leftover capecitabine tablets for 25 patients were reused at the outpatient pharmacy clinic at a cost of JPY 604142.8 (JPY 24165.7 per patient). The study results suggest that evaluating capecitabine adherence and the reasons for leftover capecitabine tablets at outpatient pharmacy clinics as well as reusing leftover medication can contribute to reducing drug costs.

Factors associated with lenvatinib adherence in thyroid cancer and hepatocellular carcinoma.

Lenvatinib is an oral anticancer medication used to treat radioiodine-refractory thyroid cancer and unresectable hepatocellular carcinoma. The purpose of this study is to evaluate lenvatinib adherence by patients and to identify factors associated with decreased lenvatinib adherence. Among 153 patients who started treatment with lenvatinib for unresectable thyroid cancer or unresectable hepatocellular carcinoma between May 1, 2015 and August 31 2021 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 102 were eligible for this study (55 thyroid cancer, 47 hepatocellular carcinoma). The lenvatinib adherence rate in a treatment cycle was defined as the number of times a patient took lenvatinib in a 28-day cycle divided by the prescribed 28 doses. The rate was determined by pill counting and self-reporting at the pharmaceutical outpatient clinic. Reasons for non-adherence were established by interview and analyzed. The median adherence rate of lenvatinib in the first cycle was 90.1% (n = 55) in thyroid cancer and 94.9% (n = 47) in hepatocellular carcinoma. In thyroid cancer, there were 255 incidents of lenvatinib non-adherence. Non-adherence was mainly associated with bleeding events (18.6%), followed by hand-foot skin reactions (10.6%). In hepatocellular carcinoma, there were 97 incidents of non-adherence. Hypertension accounted for 20.6%, followed by hoarseness (18.6%) and diarrhea (17.5%). The adherence rate for lenvatinib in Japanese patients with thyroid and hepatocellular carcinoma in real-world clinical practice was more than 90% in this study. Hypertension was a major reason for non-adherence, followed by hand-foot skin reactions and diarrhea.

The Seven-Color FISH Analysis Can Detect the Acquisition Pattern of Complex Chromosomal Abnormalities Related to Poor Response and Prognosis in Patients with Multiple Myeloma

Introduction : The proliferation of heterogeneous clones in multiple myeloma (MM) cells is associated with progression and resistance to treatments. Chromosomal abnormalities (CAs) were one of the drivers of myeloma progression and resistance mechanisms for the treatment. Here, we developed the method of simultaneous detection of five CAs in single cell by seven colors-fluorescent in situ hybridization (FISH). With this FISH analysis, we analyzed the acquisition patterns of CAs and the relationships between complex CAs with treatment response and prognosis. Methods: Patients diagnosed as MM who provided written informedconsent to participate in the study were enrolled. All the patients were treated with three or more drug-combined treatments based on proteasome inhibitors and/or IMiDs between 2014 and 2022 in our institution. Bone marrow aspiration and biopsy were performed at the time of diagnosis and upon disease progression. Myeloma cells were isolated from bone marrow samples using anti-CD138-MicroBeads. These cells were spotted on the slide glasses. After fixation and permeabilization, cells were hybridized with 7 series of probes simultaneously to detect targeted five CAs, 1q gain, del(17p), t(11;14), t(14;18), and t(4;14). The fluorescent signals were detected by confocal microscopy (ZEISS, LSM880) (Figure 1). We counted 100 or more cells in each patient and calculated the positive ratio of the five series of CAs. The relationships between each combination of CAs and non-complete response (non-CR) status were analyzed by Mann-Whitney test. The event free survival (EFS) was analyzed by Kaplan-Meier and the significant relationships were calculated by log-rank test. EFS were estimated from the start of the treatment to the days of progression, start of next treatment, or death. This protocol was approved by the institutional review board of Japanese Foundation for Cancer Research. Result: The enrolled patients were 41 including 24 newly diagnosed (ND) and 17 relapse and refractory (RR) patients. The median age was 65.8 years (40-85) in ND patients and 70.3 years (50-85) in RR patients. In ND patients, the presence of del(17p) with t(11;14) (58%; 14/24), 1q gain with t(11;14) (50%; 12/24), and t(4;14) with t(14;16) (50%; 12/24) were frequently observed. Double positivity of t(11;14) and t(14;16) alone or in combination with other CAs and t(11;14) and del(17p) alone were associated with non-CR ( P&amp;lt;0.035 and P&amp;lt;0.041, respectively). Furthermore, patients with t(11;14) and t(14;16) alone had lower EFS (HR 5.829, 95%CI;1.539-22.07) (Table 1). In RR patients, the double positivity of del(17p) and 1q gain increased to 88% (15/17) compared to 42% (10/24) in ND patients. The double positivity of t(14;16) and t(4;14) alone or with other CAs, and triple positive CAs were associated with non-CR, ( P=0.048, and 0.037, respectively). Patients with 1q gain and t(4;14) alone or with other CAs (HR 6.977, 95%CI;1.464-33.26 ) and triple positive CAs had lower EFS (HR 7.781, 95%CI; 0.98-61.76); Among triple positive CAs, the combination of 1q gain, del(17p), and t(4;14) (HR 5.871, 95%CI; 1.442-23.9), as well as the combination of 1q gain, del(17p), and t(14;16) (HR 4.363 95%CI; 1.189-16) were related to lower EFS (Table 1). Conclusion: The simultaneous FISH analysis in single cells is useful for detecting the acquisition-pattern of CA in myeloma. This method is also useful even in low numbers of myeloma cells. The single CA does not always correlate to the treatment response or prognosis. The detection of the combined acquisition of CAs might be provided a novel prognosis factor.

Patient Safety Management Practiced by Pharmacy Pharmacists Using Their Training at Oncology Hospital

Recent changes in the environment surrounding community pharmacists include "follow-up after dispensing" becoming mandatory, initiation of "certified pharmacy system with specific functions," with the discussions on post-graduate training, lifelong training and specialization, refill of prescriptions, as well as pros and cons of hospital pharmacies in preparation for the 2022 dispensing fee revision. In this regard, since 2019, I have been receiving training at The Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR). In addition, to implementing community pharmacists' perspectives into collaboration between community pharmacists and hospital pharmacists, a tracing report model incorporating the Common Terminology Criteria for Adverse Events (CTCAE) ver. 5.0 has been created. And, a regimen of drugs and operation describing necessary supportive care has been published in The Cancer Institute Hospital of JFCR website. As a practice of patient safety management at pharmacies, we are working on the standardization of questionnaire criteria to assess the severity of adverse medication reactions in cancer patients and the measurement of health-related quality of life using EuroQol 5 dimensions 5-level (EQ-5D-5L), introduced with cooperation of universities, hospitals, and pharmacies. As medical care is advancing day by day, especially in cancer medication therapy, patient safety management by pharmacists becomes essential, when dealing with the complexity of administration schedule and the wide variety of side effects. For patient safety management, community pharmacists need to practice with pharmaceutical and medical knowledge, and have skills to acquire and convey information, with a researcher's perspective.

Clinical Usefulness of Postoperative Serum Carcinoembryonic Antigen in Patients with Colorectal Cancer with Liver Metastases.

Colorectal cancer with liver metastasis (CLM) has high postoperative recurrence rates; therefore, optimizing perioperative treatment is imperative. Postoperative carcinoembryonic antigen (CEA) can aid in detecting minimal residual disease in colon cancer following curative resection. This study aimed to identify the potential role of serum CEA following liver resection in patients with CLM. This retrospective study was conducted at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 2004 to 2018 and enrolled patients with CLM who underwent complete resection of primary tumors and CLM. Associations between perioperative CEA levels and characteristics of recurrence were investigated. Recurrence was detected during a median follow-up period of 90.1 months in 343 (54.2%) out of 633 analyzed patients. Patients in the postoperative CEA level > 5 ng/ml group had a significantly higher recurrence rate (75.7% versus 50.0%,p < 0.01) and shorter time until recurrence (4.4 versus 36.9 months,p < 0.01) than those in the postoperative CEA level ≤ 5 ng/ml group. Multivariate analysis revealed that postoperative CEA level > 5 ng/ml was an independent predictor, with hazard ratios of 2.77 (p < 0.01) for recurrence-free survival (RFS) and 3.18 (p < 0.01) for overall survival (OS). Additionally, RFS was significantly shorter among patients in the postoperative CEA level > 5 ng/ml group who did not have normalized CEA levels following adjuvant chemotherapy than among those in the normalized CEA group. The postoperative and post-adjuvant chemotherapy CEA levels in the CEA level > 5 ng/ml group may be predictors of RFS and OS.

Brief, manualised and semistructured individual psychotherapy programme for patients with advanced cancer in Japan: study protocol for Managing Cancer and Living Meaningfully (CALM) phase 2 trial

IntroductionManaging Cancer and Living Meaningfully (CALM) is a novel, brief and manualised psychotherapeutic intervention intended to treat and prevent depression and end-of-life distress in patients with advanced cancer. This phase...

Abstract P4-11-06: Effect of suppressed ovarian function on prognosis of premenopausal obese women with hormone receptor-positive breast cancer: A single-institute retrospective study

Abstract Background: Obesity is related to poor prognosis in pre- and postmenopausal patients with breast cancer. However, there is insufficient evidence regarding the optimal adjuvant hormone therapy for obese premenopausal women with hormone receptor-positive breast cancer. We examined the impact of ovarian function suppression (OFS) on the prognosis of obese women with primary hormone receptor-positive breast cancer. Methods: We retrospectively reviewed premenopausal women who received curative surgery for clinical stage I-III hormone receptor (HR)-positive breast cancer at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from January 2007 to December 2017. All patients were classified into five groups according to body mass index (BMI): underweight (UW), BMI &amp;lt;18.5 kg/m2; normal weight (NW), 18.5-24.9 kg/m2; obese 1 degree (OB1), 25.0-29.9 kg/m2; obese 2 degree (OB2), 30.0-34.9 kg/m2; and obese 3 degree (OB3), ≥35 kg/m2. The primary analysis was a comparison of breast cancer-specific survival (BCSS) according to BMI (UW/NW vs. OB1-3) and adjuvant hormonal therapy (with or without OFS). Secondary endpoints included overall survival (OS). Results: Overall, the total number of patients was 13,021 and the data of 3,380 patients were analyzed, which included patients who received adjuvant tamoxifen (TAM) without OFS (n = 1,836) or with OFS (n = 670). The median follow-up duration was 5.9 years (range, 0.2-12.9). The numbers of patients with UW, NW, OB1, OB2, and OB3 were 404 (12%), 2,482 (73%), 399 (12%), 78 (2%), and 17 (1%), respectively. Obesity was significantly associated with higher stage of breast cancer (p &amp;lt;0.0001). Nuclear grade of breast cancer in OB1-3 patients was significantly higher than that in UW/NW patients (p = 0.0323). BCSS in OB1-3 patients was significantly worse than that in patients with UW/NW (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.40-4.02: p = 0.0009). In OB1-3 patients who received TAM as adjuvant hormone therapy, BCSS was significantly worse than that in UW/NW patients (p = 0.0086); however, a significant difference was not shown in patients who received TAM and OFS (p = 0.0921). Multivariate analysis revealed that OB3 was an independent prognostic factor compared with NW in patients with stage II/III breast cancer (p = 0.0162).Conclusion: High BMI was associated with worse prognosis in premenopausal patients with HR-positive breast cancer. The negative impact of obesity might be canceled by adding OFS to TAM as adjuvant hormone therapy. Further studies are required to explore the adequate management of obese premenopausal patients. Citation Format: Yukinori Ozaki, Jun Masuda, Akemi Kataoka, Takahiro Kogawa, Tomomi Abe, Hidetomo Morizono, Lina Inagaki, Fumikata Hara, Toshimi Takano, Takayuki Ueno, Shinji Ohno. Effect of suppressed ovarian function on prognosis of premenopausal obese women with hormone receptor-positive breast cancer: A single-institute retrospective study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-06.

Clinical usefulness of postoperative serum carcinoembryonic antigen in colorectal cancer patients with liver metastases.

178 Background: Colorectal cancer with liver metastases (CLM) has high post operative recurrence rates, and optimizing the perioperative treatment is imperative. Post operative carcinoembryonic antigen (CEA) can help detecting minimal residual disease in colon cancer after curative resection. Methods: The aim of this study was to identify the potential role of serum CEA after liver resection in patients with CLM. This study was conducted at the Cancer Institute Hospital, Japanese Foundation for Cancer Research from 2004 to 2018. Patients with CLM who underwent complete resection of primary tumors and liver metastases were enrolled in this study. We studied the associations between the perioperative CEA levels and characteristics of recurrence. Results: Recurrence was detected during the median follow-up time of 50.9 months in 343 (54.1%) of the total 633 patients analyzed. Patients with postoperative CEA (&gt;5) group had a significantly higher recurrence rate (75.7% vs 50.0%, p &lt; 0.01), with a shorter time until recurrence (4.4 months vs 36.9 months, p &lt; 0.01) than those with a postoperative CEA level (≤5) group. In multivariate analysis, a postoperative CEA level &gt;5 ng/ ml was an independent predictor, with the highest hazard ratio for both recurrence free survival (RFS) and overall survival (OS) (RFS: 2.77, 95% confidence interval [CI] 2.14–3.60, p &lt;0.01, OS: 3.18, 95% CI 2.41–4.19, p &lt;0.01). In addition, there was a significantly shorter RFS in the postoperative CEA level (&gt;5) group who did not have normalized CEA levels after adjuvant chemotherapy compared to normalized CEA group (3.3 months vs 18.5 months, p = 0.008). Conclusions: The postoperative CEA and postadjuvant chemotherapy CEA level in the CEA level (&gt;5) group after surgery may be a predictor of RFS and OS.

High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis.

Myxoid liposarcoma (MLPS) is genetically characterized by FUS‐DDIT3 or EWSR1‐DDIT3 gene fusion and the high frequency of hotspot mutations (C228T or C250T) in the promoter region of telomerase reverse transcriptase (TERT) that encodes the TERT protein. The latter leads to telomerase reactivation, a mechanism of telomere maintenance. Although the TERT promoter hotspot mutation is a poor prognostic factor in various tumors, its effect on MLPS has not been reported in detail. In the present study, we examined the clinicopathological characteristics, prognosis, and telomere maintenance mechanisms in 83 primary tumor samples of MLPS, which were resected surgically at the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, from 2008 to 2020. TERT promoter hotspot mutations were observed in 77% (63/82) cases, and alternative lengthening of telomeres (ALT) was absent in all cases. Among the cases without TERT promoter hotspot mutations, TERT rearrangements, and minor point mutations in the TERT promoter region were found in 3 and 2 cases, respectively. TERT mRNA expression was observed consistently even in patients for whom no genomic TERT aberrations were detected, and the presence of TERT promoter hotspot mutation did not correlate significantly with either overall and metastasis‐free survival (P = .56, P = .83, respectively) or clinicopathological features. Therefore, patients with MLPS characteristically shows TERT expression and a high prevalence of TERT aberrations. Our findings suggest that TERT aberration is not prognostic factor, but might occur at an early stage and play a key role in tumorigenesis.

The Clinical Features of Multicentric Extra-abdominal Desmoid Tumors.

Extra-abdominal desmoid tumors often occur in the necks, shoulder, chest wall, back, arm, buttock, thigh and leg. Multicentric extra-abdominal desmoids are rather rare and seem to have other clinical features. The aim of our study was to investigate clinical features, especially multicentric occurrence of extra-abdominal desmoid tumors. A total of 135 patients diagnosed with extra-abdominal desmoid were enrolled in this study from January 2005 to December 2019 at the Cancer Institute Hospital of The Japanese Foundation for Cancer Research. The operative procedure was principally wide excision. The clinicopathological factors [e.g., age, gender, pain, restriction of range of motion (ROM), tumor site, tumor size, surgical margin, multicentric occurrence, local recurrence, tumoral regression] were collected and assessed by univariate analysis. We assessed how multicentric occurrence influenced clinicopathological factors of desmoid tumors. The median follow-up was 39.9 months (range=0.29-259 months). Among 135 patients, 20 had multicentric occurrence. Multicentric extra-abdominal desmoids occurred in the neck in six cases, shoulder in four, chest wall in three, back in three, thigh in two and leg in two. In the case of multicentric occurrence on thighs and legs, tumors arose not in the anterior compartment but in the posterior compartment. Univariate analysis showed association of multicentric extra-abdominal desmoids with high local recurrence (p=0.0003), restriction of ROM (p=0.0012) and tumor size larger than 5 cm (p=0.04) but surgical margins were not correlated with local recurrence (p=0.37). Surgery should be performed in those who have severe pain or restriction of ROM. A 'Wait and see' policy is a first-line management, especially for those with multicentric extra-abdominal desmoids.

The Combined Use of 5 or More Drugs Is a Factor Related to Lower Adherence to S-1 in S-1 and Oxaliplatin Treatment for Advanced Gastric Cancer.

S-1 plus oxaliplatin (SOX) is an established treatment for advanced gastric cancer. S-1 adherence is the key to successful SOX treatment. This study focused on S-1 adherence by evaluating real-world adherence to S-1 and investigating factors related to decreased S-1 adherence. This study included cases treated between August 1, 2014 and October 12, 2016 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The S-1 adherence rate per cycle was defined as the number of times a patient took S-1/28. In this study, adherence to S-1 was assessed through pill counts and by asking the patient about the reason for non-adherence at a pharmaceutical outpatient clinic. Univariate and multivariate analyses were performed to investigate factors influencing lower adherence. This analysis included 116 patients evaluated for adherence to S-1 on SOX treatment. The median rate of adherence to S-1 was 92.8% in the first cycle and 90.5% in the seventh cycle. The median relative dose intensity of S-1 was 84.6%. In terms of reasons for nonadherence, patients most commonly cited nausea/vomiting (43.7%), diarrhea (20.8%), missed dose (11.8%), and fever (8.1%). Logistic regression analysis was performed using the most appropriate regression equation, and a significant association was detected with 1 factor, number of combined drugs ≥5 (odds ratio (OR) = 2.50; 95% confidence interval (CI), 1.04-6.03, p = 0.04). Eliminating unnecessary concomitant medications helps maintain proper adherence to S-1 in SOX treatment.

Risk factors for severe neutropenia in pancreatic cancer patients treated with gemcitabine/nab-paclitaxel combination therapy.

AimCombination therapy with gemcitabine and nanoparticle albumin-bound paclitaxel (nab-paclitaxel), known as GnP therapy, significantly prolongs the survival of pancreatic cancer patients compared with gemcitabine monotherapy. However, it may cause severe neutropenia, requiring discontinuation of treatment. This study aimed to clarify the risk factors for Grade 3/4 neutropenia during GnP therapy.MethodsClinical data of pancreatic cancer patients who underwent GnP therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from December 2014 to December 2016 were retrospectively collected. The relationship of Grade 3/4 neutropenia onset to laboratory values and patient background factors was investigated by multivariate logistic regression analysis.ResultsClinical data of 222 patients were analyzed. Grade 3/4 neutropenia occurred in 118 patients (53.2%) in the first cycle of GnP therapy. Multivariate analysis identified low absolute neutrophil count (ANC), high total bilirubin (T-Bil), and low C-reactive protein (CRP) as risk factors for Grade 3/4 neutropenia. Age was not a risk factor. The incidence of neutropenia was 85.7% in patients with all three risk factors, but only 27.7% in patients with none of them.ConclusionLow ANC, high T-Bil, and low CRP may be risk factors for Grade 3/4 neutropenia in patients receiving GnP therapy, even if these laboratory values are within normal reference ranges. Patients with these risk factors should be carefully monitored for adverse events.

Research work of Prof. Yoshioka on high-dose-rate brachytherapy monotherapy for prostate cancer

Prostate cancer is one of the most common types of cancer. If identified early, treatment can be very effective, but morbidity rates are higher in older patients and in cases where the cancer is identified in the later stages. Three main treatment options are surgery, external beam radiotherapy and brachytherapy. Professor Yasuo Yoshioka, Radiation Oncology Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, believes brachytherapy to be the most effective treatment option for prostate cancer patients and is working to improve the methods by which brachytherapy is performed in order to further enhance its effectiveness, while reducing the amount of damage to the patient during the course of treatment. Yoshioka and his team are focused on high-dose-rate (HDR) brachytherapy as they believe it has advantages over low-dose-rate (LDR) brachytherapy, including its ability to treat advanced-stage patients, the ability to adjust the strength of radiation at each source position and the fact that no radiation sources will be left in the patient's body after treatment. Yoshioka reported the world's first HDR monotherapy experience for prostate cancer and, over the past decade, he and his team have been refining the procedure in order to maximise the effect of the treatment while minimising damage to the patient.

Comparison of triweekly cisplatin regimens in definitive chemoradiotherapy for locally advanced head and neck cancer: A propensity score matching analysis.

e18007 Background: Concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) is a standard treatment for locally advanced head and neck cancer (LAHNC) in the definitive setting. Three cycles of 100 mg/m2 CDDP for every three weeks (Q3W) are now recommended but compliance with CCRT is relatively low due to its severe toxicity. Therefore, the potential de-escalation strategies for LAHNC have been discussed to decrease the therapeutic toxicity. Methods: Patients with LAHNC who underwent definitive CCRT with CDDP between 2012 and 2018 at The Cancer Institute Hospital of Japanese Foundation for Cancer Research were analyzed. Patients were classified into two groups based on the planned CDDP dose: (A) 100 mg/m2 and (B) 80 mg/m2 Q3W for three times. One-to-one propensity score matching was performed to minimize bias between two groups. After patients in two groups were matched by using propensity score, the overall survival (OS), recurrence-free survival (RFS), local recurrence-free survival (LRFS), and metastatic recurrence-free survival (MRFS) were analyzed by the Kaplan-Meier method with the Cox proportional hazards model. The follow-up term was set as two years to evaluate the early survival benefit. The dose and density of CDDP and the objective adverse events were also assessed. Results: A total of 304 patients were included with the median age of 62 (Interquartile range [IQR]: 54-67) years. Among them, 249 patients (82%) were male. Patients were treated with 100 mg/m2 CDDP (n = 145) and 80 mg/m2 CDDP (n = 159) regimens. After the propensity score matching, 119 patients were included in each group, respectively. There were no significant differences in baseline characteristics between two propensity-matched cohorts. The median follow-up time was 24 months in each group. Two-year OS was 93.0% (95% confidence interval [CI]: 88.4-97.8) in group A and 94.9% (91.0-99.0) in group B. Two-year RFS was 86.5% (80.6-92.9) in group A and 83.1% (76.6-90.1) in group B, respectively. No significant difference was observed in OS (Hazard ratio [HR] = 1.42, 95% CI: 0.49-4.08, p = 0.52), RFS (HR = 0.81, 95% CI: 0.42-1.57, p = 0.54), LRFS (HR = 0.57, 95% CI: 0.24-1.36, p = 0.20), and MFS (HR = 1.32, 95% CI: 0.52-3.35, p = 0.56). The median cumulative dose of CDDP was significantly higher in group A (300 mg, interquartile range [IQR]: 240-300) than in group B (240 mg, IQR:160-240) but the frequency of hematological, hepatic, renal, electrolytic, and grade 3-5 any adverse events was not significantly different between two groups. Conclusions: Our study showed no survival difference at 2-year follow-up between 100 mg/m2 and 80 mg/m2 CDDP regimens of definitive CCRT for LAHNC. This result could support the tide of the de-escalation strategy in head and neck cancer treatment. Longer follow-up is necessary and further prospective trials comparing CDDP dosage are warranted.

Ki-67 Labeling Index Variability Between Surgically Resected Primary and Metastatic Hepatic Lesions of Gastroenteropancreatic Neuroendocrine Neoplasms.

Background. A higher Ki-67 labeling index is associated with a poorer prognosis in gastroenteropancreatic neuroendocrine neoplasms. It has also been proposed that the Ki-67 labeling index may increase during disease progression from the primary site to metastatic sites. Although biopsy specimens are used to measure the Ki-67 labeling index, heterogeneity in lesions is thought to affect the assessment of the Ki-67 labeling index. To overcome tumor heterogeneity, we evaluated the variability in the Ki-67 labeling index between primary lesions and hepatic metastases by analyzing only surgically resected specimens. Methods. We conducted a single-center retrospective study to analyze the variability in the Ki-67 labeling index and the change in tumor grade between the primary site and metastatic hepatic sites in 19 patients diagnosed with gastroenteropancreatic neuroendocrine neoplasms at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 1998 to 2018. Both the primary site and metastatic hepatic sites were surgically resected. Results. Among the 19 patients with gastroenteropancreatic neuroendocrine neoplasms, 12 patients (63%) showed higher levels of the Ki-67 labeling index at metastatic hepatic sites than at the primary site. The median Ki-67 labeling index levels for the primary lesion and metastatic hepatic lesions were 5% and 10%, respectively. The Ki-67 labeling index levels were significantly elevated in the metastatic hepatic lesions compared to the primary lesion (P = .002). Conclusions. This study addressed the heterogeneity of the Ki-67 labeling index by analyzing only surgically resected specimens. We observed a statistically significant increase in the Ki-67 labeling index in hepatic metastases compared to the primary lesion.

Clinical influence of switching companion diagnostic tests for EGFR-TKs from Therascreen to Cobas v2.

BackgroundSeveral companion diagnostic (CDx) tests for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have been approved. In our institute, the CDx test for EGFR‐TKIs was changed from the Therascreen test (Therascreen) to the Cobas EGFR v2 test (Cobas) because only Cobas was approved for the use of osimertinib in patients with EGFR‐mutated non‐small cell lung cancer (NSCLC) with T790M mutations. The clinical influence of switching the CDx test has not yet been examined comprehensively.MethodsAll serial patients with lung cancer tested for EGFR mutations with CDx tests between February 2014 and February 2016 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR) were enrolled in this analysis.ResultsTherascreen was used as a CDx test for EGFR‐TKI therapy in 607 patients between February 2014 and January 2015, and Cobas was used in 621 patients between February 2015 and February 2016. EGFR mutations were detected in 218 patients (35.9%) and 244 patients (39.3%) tested with Therascreen and Cobas, respectively. At the initial diagnosis, 400 and 459 patients were tested with Therascreen and Cobas, respectively. EGFR mutation subtypes, including del19, L858R, and others, were detected in 13.0%, 17.0%, and 2.5% of patients using Therascreen and 17.4%, 14.4%, and 1.5% of patients using Cobas, respectively.ConclusionsNo significant impact of switching from Therascreen to Cobas as the CDx test for EGFR mutations in clinical practice was observed. However, the detection pattern of the EGFR mutation subtypes between the two CDx tests was slightly different.Key pointsSignificant findings of the studyWe examined the influence of changing the EGFR test in 1228 patients in total. The detection rate of EGFR mutations was similar. However, the detection pattern for EGFR subtype mutations was slightly different between the two tests.What this study addsSwitching CDx tests from target polymerase chain reaction (PCR)‐ to next‐generation sequencing (NGS)‐based methods may lead to obvious changes in clinical practice. When the CDx test is required to change, the investigation of this influence is warranted in future studies.

Protocol for a multicentre, prospective, cohort study to investigate patient satisfaction and quality of life after immediate breast reconstruction in Japan: the SAQLA study

IntroductionThe aim of breast reconstruction (BR) is to improve patients’ health-related quality of life (HRQOL). Therefore, measuring patient-reported outcomes (PROs) would clarify the value and impact of BR on a...

Detection of multiple intramucosal signet-ring cell carcinomas by white-light endoscopy and magnifying endoscopy with narrow-band imaging in a hereditary diffuse gastric cancer patient with a CDH1 germline mutation.

Detection of multiple intramucosal signet-ring cell carcinomas by white-light endoscopy and magnifying endoscopy with narrow-band imaging in a hereditary diffuse gastric cancer patient with a CDH1 germline mutation.