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535 Background: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. Tumor shrinkage is achieved, and cancer- and treatment-free status is possible in many cases using curative conversion with resection, ablation, or selective transarterial chemoembolization (TACE). This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter study was conducted to clarify the value of curative conversion in intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. Cancer-free rate, treatment-free rate, time to cancer-free status, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, recurrence-free survival (RFS), and overall survival (OS) were assessed in patients who achieved cancer-free status using resection, ablation, selective TACE, or atezolizumab plus bevacizumab alone. Results: Cancer-free status was achieved in 38 patients (35%) (median observation period: 17. 7 months). The modalities of curative conversion were as follows: resection, 7; ablation (including patients who underwent ablation after TACE), 13; and selective TACE (including lenvatinib-TACE sequential therapy), 15. Three patients achieved cancer-free status with only atezolizumab plus bevacizumab therapy. Among the 38 cancer-free patients, 24 achieved treatment-free status. RF5 was 31.8 months (95% confidence interval, 30.5-33.0), and two patients experienced recurrence after reaching cancer-free status. Regarding OS, there were no deaths in any of the groups, and excellent outcomes were obtained. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved cancer-free status, five achieved treatment-free status. Conclusions: The curative conversion rate (cancer-free rate) in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 22% of patients achieved treatment-free status. Thus, achieving cancer-free and/or treatment-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread. Clinical trial information: NCT03434379 .

692 Background: Patients with ampulla of Vater carcinoma with lymph node metastasis reportedly have a poor prognosis and require postoperative adjuvant therapy. However, due to the small number of published cases, the efficacy of postoperative adjuvant therapy has not yet been established with a high level of evidence. Objective: The aim of this study was to describe the outcome of patients surgically treated for ampulla of Vater carcinoma in our department, evaluate the effectiveness of adjuvant chemotherapy (AC), and clarify which patient groups may benefit from AC. Methods: The study cohort comprised 46 patients who underwent surgery for ampulla of Vater carcinoma in our department from October 2005 to March 2022. We evaluated the clinicopathological background characteristics (tumor size, gross morphology, pancreatic/duodenal invasion, peripancreatic head lymph node metastasis), overall survival (OS), and relapse-free survival (RFS), and compared the OS and RFS in patients with versus without AC. We then analyzed the factors related to the long-term outcome of patients treated for ampulla of Vater carcinoma. Results: During a median observation period of 33.7 months, the 5-year OS and RFS were 63.1% and 61.7%, respectively. Recurrence was observed in 14 patients (30%), with recurrence occurring less than 1 year postoperatively in seven patients (15%). Fifteen patients received AC (chemotherapy regimen: S-1 in 11 patients, GEM in four). The 5-year OS rates with and without AC were 70.3% and 48.2%, respectively (p=0.093). The 5-year RFS rates with and without AC were 72.5% and 42.8%, respectively (p=0.058). Univariate analysis of the total patient cohort showed that the factors related to 5-year RFS were pancreatic invasion (p=0.01), duodenal invasion (p=0.03), and N+ (p=0.004). In multivariate analysis, the only factor related to 5-year RFS was N+ (HR 3.53; 95% CI, 0.99–12.6; p=0.03). The 5-year OS rates in patients with and without N+ were 77.1% and 42.7%, respectively (p=0.04). The 5-year RFS rates in patients with and without N+ were 80.4% and 32.1%, respectively (p=0.004). Conclusions: AC showed a tendency to be effective in preventing postoperative recurrence of ampulla of Vater carcinoma. AC may be particularly beneficial in N+ cases.

460 Background: The number of overweight patients with gastric cancer who underwent gastrectomy has increased in Japan. In addition to obesity, sarcopenia is a risk factor of severe surgical complication. The study aimed to elucidate the relationship between body composition and surgical outcome of gastrectomy for gastric cancer. Methods: This study was a retrospective, cohort study that include 701 patients who underwent gastrectomy in our institution between May 2008 and July 2017. Using preoperative computed tomography (CT), body composition such as psoas muscle index (PMI) and visceral fat area (VFA) were measured in the third lumber section. The patients were divided into two groups according to PMI (cut-off value 5.2 cm2/m2 in male and 3.5 in female) or VFA (cut-off value 155 cm2 in male and 116 in female), respectively. Surgical outcomes and postoperative complications were compared between the low and high groups for each PMI and VFA value. Results: There were 53 severe complications (14 anastomotic leakage, 14 pancreatic fistula, 8 respiratory failure, and 7b intraabdominal abscess) in this cohort. Some 701 patients were included in the study, 528 of whom were classified as normal PMI and 173 were as low PMI. In addition, 528 of whom were classified as normal VFA and 173 were as low PMI. In multivariate analysis, age and gender were independent risk factor for severe postoperative complication, however, low PMI was not. Conclusions: Our analysis showed no relationship between preoperative low PMI and postoperative complications. [Table: see text]

1049 Background: Asymptomatic metastatic breast cancer (mBC) is often detected using tumor marker or imaging tests in Japan. At the ASCO 2019, we reported on mBC detection, the distribution of symptomatic and asymptomatic disease by subtype (abstract e12568). We aimed to determine whether there are differences in post-recurrence survival (PRS), and treatment between asymptomatic and symptomatic MBCs, and identify factors associated with PRS. Methods: We performed a multicenter, retrospective analysis of patients with mBC treated in our hospitals from 2008 to 2018. Patients were divided into asymptomatic and symptomatic MBCs to compare their prognosis by breast cancer (BC) subtypes: luminal (hormone receptor positive/human epidermal growth factor 2 [HER2] negative), HER2 (any hormone receptor/HER2 positive), and triple-negative (TN) (hormone receptor negative/HER2 negative). Results: Of 204 patients with mBC (114 asymptomatic, 90 symptomatic), PRS was longer in asymptomatic mBC than in symptomatic mBC (median survival: 55 months vs. 29 months; p < 0.001) and tended to have longer overall survival (OS) (110 months vs 72 months, respectively; p = 0.09). In multivariate analysis, TN, recurrence-free survival (RFS), multiple metastasis sites, and symptomatic disease were independently predictive of PRS (Table). In luminal and HER2, PRS trended higher in the asymptomatic group than in the symptomatic group (luminal: 54 months vs. 41 months; p = 0.08, HER2: 71 months vs. 27 months; p = 0.09), but without significant difference in OS (luminal: 112 months vs. 124 months; p = 0.91, HER2: 113 months vs. 72 months; p = 0.40). In the luminal group, 13 patients (11%) were treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. The median PRS was 80 months for luminal patients with three factors — longer than 4 years of RFS, a single metastasis site, and asymptomatic disease. The duration of endocrine therapy did not differ between groups; however, the patients with luminal BC in the asymptomatic group had longer chemotherapy than those in the symptomatic group. In TN, PRS was very short (asymptomatic, 28 months; symptomatic, 10.5 months; p = 0.01). Conclusions: We demonstrated that asymptomatic MBC and symptomatic MBC differed in terms of subtypes, prognosis, and duration of chemotherapy in the luminal group. Therefore, unique treatment strategy for asymptomatic or symptomatic MBC should be developed. [Table: see text]

12103 Background: Stomatitis, a frequent adverse event in patients undergoing chemotherapy, can lead to pain, ulcers, bleeding, and malnutrition due to reduced oral intake, which not only deteriorates quality of life but may also result in dose reduction or interruption of chemotherapy. However, there is currently no standard approach for preventing chemotherapy-induced stomatitis. Therefore, this study aimed to assess the efficacy and safety of a dexamethasone-based mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. Methods: We conducted a multicenter, randomized, controlled phase II trial. Patients with early-stage breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapies were allocated in a 1:1 ratio to the intervention and control groups. The sample size was set to 120 cases based on the following assumptions: stomatitis incidence of 50% in the control group and 30% in the intervention group, alpha error of 0.2, one-sided power of 0.9, and dropout proportion of 10%. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash (10 mL, 0.1 mg/mL; swish for 2 min and spit, 4 times daily for 9 weeks), and the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis that was compared between the two groups. Results: There were 60 patients in the control group and 61 in the intervention group. One patient in the control group and two in the study group withdrew consent; one patient in the control group was excluded because of discontinuation of the first cycle of chemotherapy and unavailability of data related to the incidence of stomatitis. Finally, the data of 58 patients in the control group and 59 in the intervention group were analyzed. There were no differences in age and chemotherapy regimens between the groups. The incidence of stomatitis was 55% in the control group and 38% in the intervention group (risk ratio 0.68; 80% confidence interval, 0.52 – 0.88; p = 0.052). The grade of stomatitis (0/1/2/3) was significantly lower in the study group (intervention group vs. control group: 37/13/7/2 vs. 26/16/7/9, p = 0.03). There were no differences in the duration of stomatitis between the groups. Moreover, the percentage of patients who adhered to the mouthwash regimen was 87% (range, 14% – 100%). There were no significant differences in the occurrence of other adverse events between the groups, and only one case of oral candidiasis was observed in the intervention group. Conclusions: Dexamethasone-based mouthwash safely reduced the incidence and severity of stomatitis in patients receiving chemotherapy (EC/TC) for early breast cancer. Clinical trial information: UMIN000030489.

458 Background: In the Phase III REFLECT trial, lenvatinib was superior to sorafenib in progression-free survival (PFS), time to progression, and objective response rate (ORR). This trial aimed to assess the efficacy of lenvatinib to achieve conversion surgery for initially unresectable hepatocellular carcinoma (HCC). Methods: In this multicenter prospective single-arm trial, not only technically unresectable cases but also oncologically unresectable cases were included. The oncologically unresectable cases, i.e., technically resectable but with poor prognosis, were defined as cases with macroscopic vascular invasion and/or extrahepatic metastasis. Patients eligible for the present study were treated with lenvatinib. Dynamic CT or MRI was performed every 4 weeks. After 8 weeks of lenvatinib therapy (protocol therapy), the patients were assessed for resectability, and tumor resection was performed after off of lenvatinib for 1 week or more if the tumor was considered resectable. The primary end point of the trial was the resection rate. The secondary end points were curative resection rate, overall survival time (OS), ORR, PFS, ICG retention rate at 15 minutes after lenvatinib therapy, and the resection rate after completion of protocol therapy. The trial is registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients from 11 centers were enrolled in this trial. One patient who died because of an accidental trauma immediately after study enrollment was excluded. The complete response (CR) and partial response (PR) rate of the 48 patients were 0% and 13% based on RECIST and 2% and 35% based on mRECIST, respectively. An R0, R1, and R2 resection was performed in 27 (56%), 2 (4%), and 4 patients (8%), respectively. Among the 15 unresected cases, the reasons for not undergoing surgery were inadequate response to lenvatinib in 10 patients (21%), decline of performance status in 2 patients (4%), refusal of surgery in 2 patients (4%), and worsening of comorbidities in 1 patient (2%). Postoperative 90-day mortality was not observed in any patients. Complications ≥grade III according to the Clavien-Dindo classification included bile leakage in 4 patients (8%) and intra-abdominal abscess in 3 patients (6%). The 1-year OS rate was 75.9%. Conclusions: This trial, which was the first prospective trial assessing conversion surgery, demonstrated the feasibility of conversion surgery after lenvatinib therapy in patients with initially unresectable HCC. The response rate of lenvatinib was similar to that of the REFLECT trial. Postoperative complications directly related to the administration of lenvatinib were not observed, suggesting the safety of preoperative lenvatinib therapy. Clinical trial information: jRCTs031190057.

e12568 Background: Early breast cancer (BC) patients in Japan can receive a follow-up CT scan, which can diagnose asymptomatic metastatic (M)BC. How symptomatic and asymptomatic MBC differ regarding prognosis and whether treatment strategies should differ is unclear. Methods: A retrospective, multicenter, cohort study was performed. We reviewed records of MBC women treated at four institutions between 2008 and 2018. Follow-up CTs were not routinely performed. Patients were divided into three BC subtypes: Luminal (ER+, PgR+, or both, but HER2-), HER2 (HER2+), and triple negative (TN) (ER-, PgR-, HER2-). Results: Of 205 MBC patients, 120 were luminal, 51 HER2, and 34 TN. Ninety were diagnosed with symptomatic and 115 with asymptomatic MBC. Symptomatic MBC patients had the following symptoms: locoregional metastasis (43%), bone pain (25%), cough or dyspnea (16%), and brain-related symptoms (10%). Diagnosis of asymptomatic MBC was based on follow-up imaging (71%) and elevated tumor markers (27%). The proportion of the patients with symptomatic MBC were different in each subtype: 38% luminal, 45% HER2, and 65% TN (p = 0.02). Among luminal patients, median overall survival (OS) after metastasis was longer for those with asymptomatic versus symptomatic MBC (62 vs 41 M, respectively; p = 0.04), although disease-free interval (48 vs 54 M, respectively; p = 0.40) and OS after breast surgery (119 vs 126 M, respectively; p = 0.93) did not differ significantly. Conversely, among TN patients, those with asymptomatic MBC had significantly longer median OS after metastasis and after breast surgery. Although the median period of cumulative endocrine therapy after metastasis did not differ between groups, luminal BC patients with asymptomatic MBC received chemotherapy longer than those with symptomatic MBC (20 vs 12 M, respectively; p = 0.02). Most patients switched to chemotherapy because of endocrine resistance without life threatening disease. To diagnose asymptomatic MBC might lead to longer use chemotherapy. Conclusions: Physicians should take symptomatic versus asymptomatic MBC into consideration in predicting prognosis to optimize treatment strategies.

e21668 Background: Dysgeusia is a common side effect of chemotherapy (CT) and often impacts negatively on QOL. This study analyzed the prevalence of gustatory test abnormalities in breast cancer (BC) patients undergoing CT. Methods: We enrolled 33 BC patients who were undergoing CT (26 adjuvant CT and 7 CT for advanced BC) and conducted 2 gustatory tests on CT day. In the test of sensitivity using the instillation method (IM), 4 basic taste stimuli (sweet, salty, sour, and bitter) at 5 concentrations were applied to the entire oral cavity. For the electrogustometry method (EM), we measured the amount of current for perception of metallic tastes, examining the front two thirds of the tongue (cranial nerve VII) and the back third of the tongue (cranial nerve IX). We compared awareness of dysgeusia with results of the 2 gustatory tests. Results: Median CT duration was 83 days (12–1,353). Fifteen (45%) patients had awareness of dysgeusia (Grade 1: 11, Grade 2: 4). IM revealed 8 (24%) patients with abnormalities, 7 in a single taste species and 1 in 3 taste species. EM revealed 20 (61%) patients withabnormalities, 7 in the cranial nerve VII and 20 in the cranial nerve IX innervation area. All patients with abnormalities in the cranial nerve VII innervation area also had abnormalities in the cranial nerve IX innervation area. Among 15 patients with awareness of dysgeusia, there were 5 (33%) IM abnormalities and 12 (80%) EM abnormalities (4 in the cranial nerve VII and 12 in the cranial nerve IX innervation area). Among 18 patients without awareness of dysgeusia, there were 3 (16%) IM abnormalities and 8 (44%) EM abnormalities (3 in the cranial nerve VII and 8 in the cranial nerve IX nerve innervation area). Patients with IM abnormalities had a higher frequency of abnormalities in the cranial nerve VII innervation area than the normal range (50% and 12%, respectively; p = 0.04); there was no significant difference in the cranial nerve IX innervation area. Conclusions: Nearly half of the patients reporteddysgeusia, but most of these could correctly identify the four basic tastes. Further studies to clarify the discrepancy between subjective and objective observations could lead to effective prevention and treatment of dysgeusia.

e17556Background: In patients with papillary thyroid carcinoma (PTC), the role of total thyroidectomy (TT) versus that of thyroid lobectomy (TL) has been controversial. Patients who undergo TT are ...

e14548 Background: We conducted a central review of liver resectability and pathological response for two Phase II trials for initially unresectable, or not optimally resectable, colorectal cancer ...

e20670 Background: We previously reported that compression and medication therapies applied to breast cancer patients 1) control chemotherapy-induced peripheral neuropathy (CIPN) grades, and 2) inc...

587 Background: Exploratory biomarker studies in the randomized phase III PRIME study suggested that patients with mCRC tumors harboring a mutation (MT) in KRAS or NRAS (beyond KRAS exon 2) do not respond to panitumumab-FOLFOX4 (2013 ASCO, JCO 31, #3511). We reported the efficacy and safety of S-1+. Cetuximab (Cmab) in wild-type (WT)-KRAS (exon 2) mCRC patients (pts) as third-line therapy (KSCC0901) (2012 ASCO, JCO 30, s3558). The full spectrum of characterized RAS (KRAS and NRAS), PI3CA, and BRAFMTs may affect efficacy in S-1+Cmab therapy in Japanese patients. Methods: An analysis was conducted to assess the treatment effect of S-1+Cmab, according to RAS (KRAS and NRAS), PI3CA, and BRAF MTs. The treatment protocol of KSCC0901 was as follows: weekly intravenous Cmab administration of 400 mg/m2 (day 1), 250 mg/m2/week (following day 1) and oral administration of 80 mg/m2/day S-1 on days 1–28 of each 42-day cycle. MTs in KRAS codons 12 and 13 (exon 2) were detected using direct sequencing according to the manufacturer’s instructions. MTs in KRAS codons 61 and 146, NRAS codons 12, 13 and 61, BRAF codon 600 and PIK3CA codons 542, 545, 546, and 1047 were detected using the multiplex PCR-Luminex method-based MEBGEN MT Kit (Medical and Biological Laboratories, Nagoya, Japan). Results: 35 pts were eligible for the analysis. Number of MT cases of KRAS, NRAS, BRAF, and PIK3CA were 4, 2, 2, and 5, respectively. One case had MTs of NRAS and PIK3CA. In 37 cases with WT KRASexon2 pts, median progression-free survival (mPFS) was 5.6 [95% CI: 4.4 – 5.7] months; median overall survival (mOS), 13.5 [8.5-16.5] months; and best overall response (ORR), 37.8%. In the all-WT subgroup 23 cases, mPFS was 5.6 [5.1-7.1] months; mOS, 13.5 [9.3-21.2] months; and best ORR, 47.8%. In 12 patients with any MT, mPFS was 4.0 [2.7-7.5] months; mOS, 5.5[2.9- ] months; and best ORR, 16.7%. Conclusions: These results suggest that also in Japanese patients receiving a Cmab containing regimen, RAS, BRAF and PIK3CA MT status beyond KRAS exon2 might predict non-responders to treatment. Clinical trial information: UMIN000002475.

e14633 Background: Kyushu Study group of Clinical Cancer (KSCC) conducted the phase II study that evaluated the neoadjuvant chemotherapy for optimally-unresectable colorectal liver-limited metastases (KSCC0802, Samura et al, J Clin Oncol 30:4s, 2012). We carried out a central review for the purpose of obtaining an objective assessment of how resectability changed during treatment. Methods: We reviewed the CT or MRI images before and after protocol treatment, according to the method of CELIM study. A surgical review was done by five independent hepatobiliary special surgeons from five different centers. A resectability was reviewed based on radiological images only. Individual surgeons were blinded to the time when the CT scan was taken. The surgeons voted for (1) curative resection, (2) exploratory laparotomy with aim of resection (3) borderline resectable with chemotherapy preferred first, (4) unresectable, (5) non-evaluable. Patients were considered resectable if 50% (non-evaluable is excluded) or more of surgeons voted for categories (1) and (2), and images were considered evaluable if more than three surgeons voted with categories (1)–(4). Results: In KSCC0802 study, of the 40 pts. enrolled from Sept. 9 2008 to Aug. 10 2010. The number of cases to intent operation after chemotherapy was 17 (42.5%), and the actual liver resectability was 16/40 (40.0 %). The number of R0 cases was 10 pts. . In total, 77 images were presented for this central review. Only three follow-up scans were not available. Following review, 17 (42.5%) of 40 patients were judged to be resectable after chemotherapy, compared with 14 (35.0%) patients at baseline. Of 36 cases in which both imaging studies were available to be evaluated before and after chemotherapy, 7 cases (19.4%) judged as unresectable before chemotherapy were finally determined as resectable after chemothrerapy. Conclusions: With the central review by 5 independent liver surgeons, the resectability was fairly determined before and after chemotherapy. mFOLFOX6 with Bevacizumab regimen is safe and effective for unresectable liver limited-metastases from colorectal cancer, and might be to lead the liver resectability. Clinical trial information: UMIN000001308.