Courses Of Neoadjuvant Chemotherapy Research Articles

Randomized phase III trial of neo-adjuvant and adjuvant chemotherapy vs adjuvant chemotherapy alone for localized soft tissue sarcoma (NACLESS, JCOG2102).

TPS11589 Background: Soft-tissue sarcomas (STS) are a rare malignant tumor. Adjuvant perioperative chemotherapy has been investigated for high-risk patients due to the poor overall survival (OS) for surgery. A meta-analysis revealed that adjuvant chemotherapy (AC) with doxorubicin plus ifosfamide (AI) significantly prolonged OS with an absolute risk reduction of 11%. However, the optimal timing for surgery and number of courses of chemotherapy are still controversial. In Europe, Italian sarcoma group and the Spanish sarcoma group reported on the non-inferiority of three courses of neoadjuvant chemotherapy (NAC) + surgery without AC, compared to three courses of NAC + surgery + two courses of AC. On the other hand, even in the same Europe, the latest report on perioperative chemotherapy with AI from Germany was a trial of surgery + AC. Furthermore, adjuvant chemotherapy itself remains skeptical in other countries such as the US, UK, and Canada. No investigation has been made into whether chemotherapy/surgery are better to initiate treatment with. In Japan, the standard treatment is three courses of NAC with AI, surgery, and two of AC with AI. However, in JCOG1306, NAC was discontinued in 12 of 70 (17.1%) patients due to high toxicity. Only one patient (1.4%) became partial response after NAC, whereas six patients (8.6%) had disease progression during NAC. Of the 65 patients eligible for limb-sparing surgery at enrollment, three (4.6%) underwent limb amputation. Upfront surgery followed by three courses of AC was considered the most promising treatment, it avoided extended surgery and reduced toxicity while maintaining an OS equivalent to the standard treatment. The aim of this trial is to optimize the balance between the survival benefit of perioperative chemotherapy, reduce toxicities, and risks of extended surgery. Methods: This is a multicenter two-arm open-label randomized phase III trial. Patients are randomly assigned to standard (three courses of NAC, surgery, and two of AC) or experimental (surgery and three courses of AC) arms with AI comprising doxorubicin (30 mg/m2, days 1, 2) and ifosfamide (2 g/m2, days 1–5). Major inclusion criteria were (1) spindle cell STS; (2) T2-4N0M0 (UICC/AJCC 8th edition) and deeply located; (3) resectable tumors in the extremities or trunk; (4) age, 16–70 years; (5) ECOG performance status of 0–1; (6) no history of chemotherapy/radiotherapy; and (7) sufficient bone marrow function. To evaluates the non-inferiority in OS (margin: hazard ratio of 1.61) with power of 70% and one-sided alpha of 10%, 224 patients will be enrolled from 39 institutions in Japan. We began this study on November 16, 2022, and 27 of 224 patients have been enrolled as of January 7, 2024. Clinical trial information: jRCTs031220446 .

Predictive analysis of breast cancer response to neoadjuvant chemotherapy through plasma metabolomics.

Preoperative chemotherapy is a critical component of breast cancer management, yet its effectiveness is not uniform. Moreover, the adverse effects associated with chemotherapy necessitate the identification of a patient subgroup that would derive the maximum benefit from this treatment. This study aimed to establish a method for predicting the response to neoadjuvant chemotherapy in breast cancer patients utilizing a metabolomic approach. Plasma samples were obtained from 87 breast cancer patients undergoing neoadjuvant chemotherapy at our facility, collected both before the commencement of the treatment and before the second treatment cycle. Metabolite analysis was conducted using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry (LC-MS). We performed comparative profiling of metabolite concentrations by assessing the metabolite profiles of patients who achieved a pathological complete response (pCR) against those who did not, both in initial and subsequent treatment cycles. Significant variances were observed in the metabolite profiles between pCR and non-pCR cases, both at the onset of preoperative chemotherapy and before the second cycle. Noteworthy distinctions were also evident between the metabolite profiles from the initial and the second neoadjuvant chemotherapy courses. Furthermore, metabolite profiles exhibited variations associated with intrinsic subtypes at all assessed time points. The application of plasma metabolomics, utilizing CE-MS and LC-MS, may serve as a tool for predicting the efficacy of neoadjuvant chemotherapy in breast cancer in the future after all necessary validations have been completed.

Functional hemodynamic imaging markers for the prediction of pathological outcomes in breast cancer patients treated with neoadjuvant chemotherapy.

Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes. We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT. Twenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers. Normalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles (). In addition, the change in normalized tumor upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle (). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI. These findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens.

Abstract PO3-03-12: Factors associated with response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer

Abstract Background: The addition of pembrolizumab (pembro) to neoadjuvant chemotherapy (NAC) became a standard-of-care for the treatment of early-stage triple negative breast cancer (TNBC) after the phase III KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) rates and event free survival with the combination. To date, clinical predictors of response to pembro with NAC are lacking. We sought to identify real-world clinical characteristics and treatment variables associated with response to NAC with pembro. Methods: We performed a single institution, retrospective study of early-stage TNBC patients diagnosed between February 1st, 2020 and December 1st, 2022 who were treated with NAC and pembro. Patients who had not undergone definitive surgery were excluded. Demographic information, clinical and pathologic characteristics, and treatment data were collected. pCR was defined as ypT0/Tis and ypN0. Univariate and multivariate analysis was performed using logistic regression to identify factors associated with pCR. This study was approved by an Institutional Review Board. Results: Of the 94 patients analyzed, 93 were female and 1 was male. The median age was 55 years (IQR 47 – 61.8) and median body mass index (BMI) was 30 (24.1-33.6). Self-reported racial/ethnic groups included 37 non-Hispanic White (39.4%), 33 Hispanic (35.1%), 13 Asian (13.8%), 7 Black (7.4%), and 4 other/unknown (4.3%). 8 (8.5%) and 2 (2.1%) of patients had deleterious germline BRCA1+ and BRCA2+ mutations, respectively. The majority of patients had invasive ductal histology (90.4%), clinical T2 stage (68.1%), and node negative (55.3%) disease. 61 (64.9%) patients completed the planned 8 cycles of NAC, while 42 (44.7%) completed the planned 8 cycles of neoadjuvant pembro. A pCR (ypT0/Tis ypN0) was achieved in 60 (63.8%) of the 94 patients. Among those who achieved a pCR, 32 (53.3%) completed the prescribed course of NAC and pembro in combination, whereas 9 (47.1%) of the 34 patients with residual disease did not. In univariate analyses, patients under 55 years at time of diagnosis (vs. age >55 years), higher ki-67, those completing the prescribed course of NAC, those completing the prescribed course of pembro, the months from start of NAC to surgery, and the months from start of pembro to surgery were associated with pCR. The duration from start of NAC or pembro to surgery overlapped considerably with the response explained by completion of NAC or pembro, respectively. Although pCR estimates were lower for Hispanic (60.6%) and non-Hispanic White patients (Black: 57.1%, Asian: 53.8%, and Other: 50%) when compared to non-Hispanic White patients (73.0%), the results were not statistically significant. In multivariate analyses, patients under 55 years at time of diagnosis (OR 3.06, 95% CI:1.18-8.0, p=0.02) and those completing the full course of pembro (OR 2.86, 95%CI: 1.08-7.58, p=0.034) had improved rates of pCR. BMI, race, BRCA1/2 status, histology, clinical T and N stage, grade, time between start/end of NAC and IO to surgery were not significantly associated with pCR on multivariate analysis. Conclusion: In our experience, younger TNBC patients were more likely to achieve a pCR with NAC with pembro. Moreover, the completion of the planned course of pembro prior to surgery was also associated with improved pCR rates. These findings suggest that adherence to neoadjuvant pembro prior to surgery may be more important than the completion of the NAC. Further research to identify the optimal exposure of NAC with pembro is needed to refine treatment recommendations in this high-risk population. Citation Format: Alexis LeVee, Megan Wong, Sarah Flores, Nora Ruel, Heather McArthur, James Waisman, Joanne Mortimer. Factors associated with response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-12.

The Role of Circulating MicroRNAs in the Prediction of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer in the Indian Population.

MicroRNAs (miRNAs) are known to play an important role in cancer cell proliferation, susceptibility of cancer cells to chemotherapy, and patient survival. Identifying miRNAs that can predict response to chemotherapy in locally advanced breast cancer (LABC), the most common variant, can help to choose appropriate drug regimensto suit the epigenetic profile of individual patients. To investigate the expression of the differentially expressed miRNAs identified by next-generation sequencing from a pilot study involving cases and controls, in peripheral blood mononuclear cells (PBMC) of patients with LABC during the course of neoadjuvant chemotherapy (NAC) and determine their role in response to chemotherapy. This study included 30 newly diagnosed LABC patients. Peripheral blood from every participant was collected before the start of chemotherapy, at the end of the third cycle, and at the end of the seventh cycle of NAC. Based on the results of a pilot study in a similar population with suitable controls, four differentially expressed miRNAs namely miR-24-2, miR-192-5p, miR-3609, and miR-664b-3p were considered to be validated in this study. The expression of these four miRNAs was examined by qRT-PCR, and their association with response to chemotherapy was analyzed. A significant change in the expression of miR-192-5p was found in responders (p = 0.001) over a period of seven cycles and the difference between the expression of miR-24-2 from baseline to the seventh cycle of NAC was higher in responders while compared to the non-responders (p < 0.05). miR-192-5p and miR-24-2 were identified as predictive biomarkers for response to NAC in south Indian patients with LABC.

Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature.

The management of hepatoblastoma (HB) becomes challenging when the tumor remains in close proximity to the major liver vasculature (PMV) even after a full course of neoadjuvant chemotherapy (NAC). In such cases, extreme liver resection can be considered a potential option. To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC. We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023. We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC. Sixty-seven children diagnosed with HB underwent surgical resection. The age at diagnosis was 21.4 ± 18.8 months, and 40 boys and 27 girls were included. Fifty-nine (88.1%) patients had a single tumor, 39 (58.2%) of which was located in the right lobe of the liver. A total of 47 patients (70.1%) had PRE-TEXT III or IV. Thirty-nine patients (58.2%) underwent delayed resection. After a full course of NAC, 16 patients still had close PMV (within 1 cm in two patients, touching in 11 patients, compressing in four patients, and showing tumor thrombus in three patients). There were 6 patients of tumors in the middle lobe of the liver, and four of those patients exhibited liver anatomy variations. These 16 children underwent extreme liver resection after comprehensive preoperative evaluation. Intraoperative procedures were performed according to the preoperative plan, and the operations were successfully performed. Currently, the 3-year event-free survival of 67 children with HB is 88%. Among the 16 children who underwent extreme liver resection, three experienced recurrence, and one died due to multiple metastases. Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible. This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis. Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB, particularly for assessing vascular involvement, remnant liver volume and anatomical variations.

Complex Treatment of A Rare Non-Germinomatous Germ Cell Optic-Chiasmal Brain Tumor In An Adolescent Child-A Clinical Case With Literature Review

Non-germ cell tumours (NGCTs) are rare intracranial neoplasms occurring in adolescents and young adults. A multidisciplinary team including a neurosurgeon, oncologist, radiologist, pathohistologist, ophthalmologist, pediatric oncohematologist, neurologist and endocrinologist is required for diagnosis and treatment. We present a rarely diagnosed optic-chiasmal non-germinomatous germ cell tumour (NGGCT) in a 16-year-old boy, accompanied by pituitary insufficiency (diabetes insipidus and central hypothyroidism) and severely impaired vision bilaterally. The immunohistochemistry (IHC) of the tumor biopsy, as well as the level of tumor markers (human chorionic gonadotropin and alpha-fetoprotein) in the serum and cerebrospinal fluid are significant factors for determining the diagnosis-cranial GCT or cranial NGCT. Because the tumor was inoperable, we performed 3 courses of neoadjuvant chemotherapy followed by definitive radiotherapy to a total tumor dose of 55 Gy. In such rare childhood brain tumors, complex treatment achieves long-term local tumor control, requiring long-term monitoring by an ophthalmologist and endocrinologist.

Neoadjuvant immunochemotherapy for pulmonary large-cell neuroendocrine carcinoma: case report

BackgroundPulmonary large-cell neuroendocrine carcinoma (pLCNEC) represents a rare malignancy characterized by its aggressive behavior and a notably high recurrence rate. Remarkably, there is currently no established standard treatment protocol for this condition.Case descriptionIn this report, we present an intriguing case of pLCNEC diagnosed at clinical-stage IIB. This case involves a 64-year-old man with a smoking history spanning four decades. In our approach, we initiated a course of neoadjuvant chemotherapy in combination with pembrolizumab, administered for two cycles prior to surgical resection. This innovative treatment strategy resulted in a significant pathological response, culminating in a major pathological remission (MPR). As of the time of composing this report, the patient has been diligently monitored for 39 months post-surgery, exhibiting no indications of recurrence, and has demonstrated exceptional tolerance to the entire treatment regimen.ConclusionsWe have first reported a clinically successful case of neoadjuvant combination chemotherapy with pembrolizumab in the treatment of pLCNEC. This case offers promising clinical insights and suggests that this therapeutic approach could be a viable option for managing pLCNEC.

An international worldwide retrospective cohort observational study comparing primary cytoreductive surgery with neoadjuvant chemotherapy and interval cytoreductive surgery in patients with carcinoma of the ovary, fallopian tubes, and peritoneum (SUROVA trial)

BackgroundCurrently, a lively debate exists within the scientific community regarding the most suitable procedure for treating stages IIIB–IVB carcinoma of the ovary, fallopian tubes, and peritoneum. The options under most...

Clinico-pathological Outcomes of Muscle Invasive Carcinoma Bladder in Post Neoadjuvant Chemotherapy Radical Cystectomy

Background: Neoadjuvant chemotherapy (NAC) before radical cystectomy is advocated in patients with muscle invasive urothelial carcinoma of the bladder with the goal to improve survival by downstaging the primary tumour and eradicating micro-metastasis. The use of perioperative chemotherapy for bladder cancer, particularly in the neoadjuvant setting, remains limited. This study was designed to evaluate NAC plus RC regarding pathological response, perioperative morbidity and mortality outcomes. Methods: This is a prospective and retro prospective study that was carried out from Jan 2018 to Jan 2020 for patients with muscle invasive bladder carcinoma. All patients having operable muscle invasive bladder carcinoma, Eastern Cooperative Oncology Group (ECOG) performance status 0–1 were included. Patients found to have metastatic disease, recurrent disease, patient not able to tolerate NAC were excluded from the study. Results: Early complications occurred within 30 days after surgery &amp; pathological response rates, perioperative morbidity, and mortality were compared. Conclusions: A short course of neoadjuvant chemotherapy was associated to a low incidence of serious adverse events and did not increase the post-operative morbidity. Results suggest that non-urothelial tumour showed no response to Platinum based combination chemotherapeutic regimens. After NAC, residual local disease, persistent nodal disease and status of surgical margins are the most powerful prognostic factors for patients who underwent RC.

Different response of two primary neoplastic lesions to neoadjuvant therapy: a case report

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor, which is mostly solitary in the pancreas. Surgery-based comprehensive treatment with adjuvant chemotherapy is the currently advanced treatment modality, neoadjuvant chemotherapy has achieved satisfactory results, however, due to the high heterogeneity of PDAC, its sensitivity to chemotherapy is also different. A 66-year-old man presented with discomfort in the upper abdomen and Computed Tomography (CT) scans revealed two tumor lesions in the head and tail of the pancreas, respectively. Endoscopic ultrasonoraphy guided fine needle aspiration (EUS-FNA) was performed to clarify the pathology and the patient was recommended to undergo neoadjuvant therapy. Through five courses of neoadjuvant chemotherapy, the two tumors showed different treatment effects, and after evaluation, total pancreatectomy and splenectomy were provided to patients.We report a case of the one patient presenting with two pancreatic cancer lesions, who demonstrated different therapeutic responses after receiving neoadjuvant chemotherapy due to the heterogeneity of PDAC.

Neoadjuvant Chemotherapy Is Effective in Those Infected With SARS-CoV-2: The Real-World Experience of a Large Chinese Breast Cancer Center.

During the major shift in China's policies on coronavirus disease 2019 (COVID-19), many residents will be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over a short period, including a few patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Moreover, it is unknown whether this comorbidity affects the efficacy of NAC for breast cancer and the patient's psychological state and quality of life (QOL). This study aims to answer these questions. The clinical data of 2,793 patients with breast cancer who received NAC at The Affiliated Hospital of Qingdao University were retrospectively collected. The infected and non-infected groups were divided according to whether they were infected with COVID-19 during NAC. Propensity score matching was used to reduce patient selection bias. The effectiveness, psychological well-being, and QOL of the two groups were compared. No discernible differences were observed in the pathological complete response rates (p = 0.307) and major histological responses rate (p = 0.398) between the infected and non-infected groups. Following the full course of NAC, the Functional Assessment of Cancer Treatment General (p < 0.001) and Functional Assessment of Cancer Therapy for Breast Cancer (p < 0.001) were lower in the infected group than the non-infected group, the Hospital Anxiety and Depression Scale (HADS) anxiety scale (p < 0.001) and HADS depression scale (p < 0.001) were considerably higher in the infected group than the non-infected group. With timely treatment and effective medical management, SARS-CoV-2 does not appear to affect the efficacy of NAC; however, it can significantly affect the QOL of patients and increase their psychological distress. Therefore, in addition to a timely assessment of the efficacy of NAC, it is necessary to dynamically understand the patient's psychological state and QOL.

Protocol of a pilot randomized clinical trial to evaluate nutritional support and rehabilitation on prevention of skeletal muscle mass loss during neoadjuvant chemotherapy in patients with esophageal cancer.

Subtotal esophagectomy with lymph node dissection followed by neoadjuvant chemotherapy (NAC) is the standard treatment for stage II-III esophageal cancer. Esophagectomy is still associated with high morbidity rates, and reducing these rates remains challenging. Among several complications, postoperative pneumonia (PP) is sometimes fatal, which has been reportedly caused by sarcopenia. Thus, nutritional support and rehabilitation may be promising for preventing skeletal muscle mass loss and reduce the incidence of PP. This single-center, randomized, open-label, pilot trial will randomize a total of 40 patients with esophageal cancer in a 1:1 ratio either to ISOCAL Clear + rehabilitation arm or only rehabilitation arm. Although all patients will be educated about rehabilitation by a specialized physician and will be asked to undergo the prespecified rehabilitation program, patients treated with ISOCAL Clear + rehabilitation arm will be supplemented by 400 mL of ISOCAL Clear (Nestlé Japan Ltd, Tokyo, Japan) per day during two courses of NAC with docetaxel, cisplatin, and fluorouracil. Body composition will be assessed using Inbody (Inbody Co., Ltd., Tokyo, Japan) just before starting NAC and surgery. The primary endpoint is the change of skeletal muscle index (SMI) during NAC. Secondary endpoints include (i) body weight, total skeletal muscle mass, appendicular skeletal muscle mass, and lean body mass index changes; (ii) the percentage of ISOCAL Clear continuation; (iii) appetite evaluation; (iv) the percentage of targeted calorie achievement; (v) adverse events of NAC; (vi) postoperative complication rates; and (vii) postoperative hospital stay. This prospective trial assesses the efficacy of nutritional support in addition to rehabilitation during NAC for patients with esophageal cancer. The results will be utilized in assessing whether the effects of nutritional support by ISOCAL Clear are promising or not and in planning future larger clinical trials.

Risk factors for failing to complete gemcitabine-cisplatin neoadjuvant chemotherapy in muscle invasive bladder cancer patients.

We evaluated the risk factors associated with failure to complete gemcitabine-cisplatin (GP) neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC). In total, 231 patients with MIBC treated with NAC before undergoing radical cystectomy between 2013 and 2022 participated in this study. Logistic regression analysis was performed to assess the relationship between the likelihood of incomplete NAC and clinical and demographic variables, including age, sex, hypertension (HTN), diabetes mellitus (DM), prechemotherapy glomerular filtration rate, clinical T stage, clinical N stage, and body mass index (BMI). Of 231 patients, 209 (90.5%) and 22 (9.5%) completed and discontinued the NAC course, respectively. The mean age was 66.13±9.15, 65.63±9.07, and 70.86±8.66 years for the total sample, continuation, and discontinuation groups, respectively (p=0.010). No significant inter-group differences in sex, HTN, height, weight, BMI, pre-chemotherapy glomerular filtration rate, clinical T stage, or clinical N stage were observed. According to the results of the multivariable analysis, age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.013-1.143, p=0.018) and the presence of DM (OR 2.541, 95% CI 1.028-6.281, p=0.043) were significantly associated with NAC discontinuation. Thus, older age and presence of DM are potential risk factors for GP NAC discontinuation in patients with MIBC. Further studies are required to validate our findings and develop strategies to minimize the rate of GP NAC discontinuation in this population.

3–4 Cycles versus 6 Cycles Neoadjuvant Chemotherapy in Advanced-Stage Epithelial Ovarian Cancer: Survival Is Not Determined by the Number of Neoadjuvant Chemotherapy Cycles

Introduction: The aim of this study was to compare the disease-free survival (DFS) and overall survival (OS) of patients who underwent interval cytoreductive surgery after 3–4 cycles or 6 cycles of neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer patients. Methods: Out of 219 patients with advanced epithelial ovarian cancer, 123 patients received 3–4 cycles and 96 patients received 6 cycles of platinum-based NACT. Afterward, laparotomy was performed for interval cytoreductive surgery. Results: No statistically significant difference was found for DFS and OS of the patients who received 3–4 cycles and those who received 6 cycles of NACT (HR: 1.047, 95.0% CI [0.779–1.407]; p: 0.746 for DFS, and HR: 1.181, 95.0% CI [0.818–1.707]; p: 0.368 for OS). Evaluating 123 patients who received 3–4 cycles of NACT, 87 patients (70.7%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS compared to 36 patients (29.3%) with any residual tumor (HR: 1.830, 95.0% CI [1.194–2.806]; p: 0.003 for DFS, and HR: 1.946, 95.0% CI [1.166–3.250]; p: 0.009 for OS). 96 patients who received 6 courses of NACT were evaluated; 63 patients (65.6%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS than 33 patients (34.4%) with any residual tumor (HR: 1.716, 9 5.0% CI [1.092–2.697]; p: 0.010 for DFS, and HR: 1.921, 95.0% CI [1.125–3.282]; p: 0.013 for OS). Conclusion: In patients with advanced ovarian cancer, there is no significant difference in DFS and OS between 3 and 4 cycles or 6 cycles of NACT. The most important factor determining survival is whether macroscopic residual tumor tissue remains after interval cytoreductive surgery following NACT.

Clinical impact of skeletal muscle mass change during the neoadjuvant chemotherapy period in patients with gastric cancer: An ancillary study of JCOG1002.

Recent studies have revealed that sarcopenia is associated with postoperative complications and poor prognosis. Although neoadjuvant chemotherapy is a promising treatment for gastric cancer, its toxicity may lead to the loss of skeletal muscle mass. This study investigates the changes in skeletal muscle mass during neoadjuvant chemotherapy and its clinical impact on patients with locally advanced gastric cancer. Fifty patients who completed two courses of neoadjuvant chemotherapy followed by surgery were included. Skeletal muscle mass was measured using computed tomography images before and after chemotherapy. The proportion of skeletal muscle mass change (%SMC) during neoadjuvant chemotherapy and its cutoff value was explored using the receiver operating characteristic for the overall survival of patients undergoing R0 resection. Risk factors of skeletal muscle mass loss were also evaluated. Overall, 64% of patients had skeletal muscle mass loss during neoadjuvant chemotherapy (median %SMC -3.4%; range: -18.9% to 10.3%). Multivariable analysis identified older age (≥70years) as an independent predictor of skeletal muscle mass loss (mean [95% confidence interval]: -4.70% [-8.83 to -0.58], p=0.026). Among 43 patients undergoing R0 resection, %SMC <-6.9% was an independent poor prognostic factor for overall survival (hazard ratio, 11.53; 95% confidence interval, 2.78-47.80) and relapse-free survival (hazard ratio 4.54, 95% confidence interval 1.50-13.81). Skeletal muscle mass loss occurs frequently during neoadjuvant chemotherapy for locally advanced gastric cancer and could adversely affect survival outcomes.

HPB P12 Do Chemotherapy Factors or Treatment Intervals Influence Pathological Tumour Response during Neoadjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma? A Bi-Institutional Study

Abstract Background Pathological response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant chemotherapy (NAT) can be assessed using grading systems such as the College of American Pathologists (CAP) system, with favourable regression being associated with improved oncological outcomes. The aim of the study was to investigate factors associated with favourable tumour regression in patients undergoing pancreatoduodenectomy (PD) for PDAC. Methods Patients who received NAT before undergoing PDAC resection at two institutions in the United Kingdom between 2013 and 2021 were reviewed. Interactions between chemotherapy regimens, tumour staging, carbohydrate antigen 19-9 (Ca19-9) levels, perioperative factors and tumour regression grading (TRG) were explored. Results 54 patients were identified who were suitable for inclusion. 12 (22%) patients had a favourable response to NAT according to the CAP grading system. A significantly greater reduction in Ca19-9 observed in the favourable TRG group [mean -2359 U/mL] compared to the unfavourable TRG group [mean -569 U/mL (p&amp;lt;0.001). The type of chemotherapy agent received, the number of cycles or whether the patient had a dose reduction during their NAT course did not differ significantly between the groups. The time from diagnosis to chemotherapy and time from end of chemotherapy to surgery were also similar between the groups. Conclusions In this bi-institutional retrospective study, neither chemotherapy factors nor treatment intervals were not found to be significantly related to pathological tumour response to NAT in PDAC patients undergoing resection. Given that a favourable pathological response has been related to improved oncological outcomes, future research should concentrate on further mechanisms that may influence the response of PDAC tumours to NAT, such as gene expression and the tumour microbiome. Given that NAT is also a relatively new approach, further multicentre collaboration should be encouraged to increase numbers of patients for study.

Experience in Using Breast Single-Photon Emission Computed Tomography with &lt;sup&gt;99m&lt;/sup&gt;Tc-MIBI

Objective: evaluation of the results of single-photon emission computed tomography (SPECT) with technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) in women with breast masses according to mammography (MMG) and ultrasound (US) examination in comparison with the results of morphology analysis.Material and methods. SPECT with 99mTc-MIBI was performed in 11 women aged from 30 to 63 years (median age 40 [33.5; 46.5]) with BI-RADS (Breast Imaging Reporting and Data System) categories 4 or 5 mammary masses according to bilateral MMG and US diagnostics. Two patients underwent repeated SPECT and US to analyze the primary tumor response to neoadjuvant chemotherapy.Results. With a multimodal approach to the diagnosis of breast tumors, including MMG and US, 11 pathological masses were identified. SPECT made it possible to find an additional mass that had not been previously visualized. All 12 masses were subsequently verified morphologically. With benign changes, hyperfixation of 99mTc-MIBI was not observed. SPECT allowed to assess the accumulation of the radiopharmaceutical in metastatically affected lymph nodes. However, the most sensitive method for detecting the axillary lymph node lesions is US. According to the results of repeated SPECT in 2 patients, no radiopharmaceutical accumulation was noted in mammary gland masses after two courses of neoadjuvant chemotherapy, but according to the histological examination, the tumor response was different: I and IV degrees of pathomorphosis according to G.A. LavnikovaConclusion. The experience of using mammary SPECT with 99mTc-MIBI confirms an increase in the accuracy of radiologic diagnosis of newly identified breast cancer, expands the possibilities of examination in cases of ambiguous MMG and US data, as well as the contraindications or patient’s refusal from magnetic resonance imaging.

A case report of long-term successful use of maintenance therapy with PARP inhibitors in the primary treatment of advanced brca-associated ovarian cancer

Background. Ovarian cancer is the third most common cancer of the female reproductive system after cervical and uterine cancer and is diagnosed at stage III–IV in 2 out of 3 cases. Maintenance therapy with PARP inhibitors signifcantly prolongs disease-free and overall survival. The purpose of the study was to demonstrate long-term remission in a patient with advanced ovarian cancer using maintenance therapy with PARP inhibitors (olaparib). Description of the clinical case. A 54-year-old female patient with verifed stage IV ovarian cancer, peritoneal carcinomatosis and left-sided pleurisy received combined modality treatment, including 2 courses of neoadjuvant chemotherapy with paclitaxel/carboplatin, cytoreductive surgery and 6 courses of postoperative chemotherapy with docetaxel/cisplatin. The patient was diagnosed with a somatic BRCA2 gene mutation (c.3708delA), which was detected by tumor DNA sequencing. The patient received maintenance therapy with olaparib for 38 months, resulting in no evidence of disease progression. Conclusion. This clinical case demonstrates the feasibility of using maintenance therapy with PARP inhibitors in a patient with initially disseminated platinum-sensitive ovarian cancer. Olaparib maintenance therapy provides stable long-term remission with no signs of adverse events and determined effect on quality of life of the patient.

Idiopathic Thrombocytopenia Purpura After Pembrolizumab Treatment Against Locally Recurrent Bladder Cancer : A Case Report

A man in his 70s visited our hospital for gross hematuria. He was diagnosed with invasive urothelial carcinoma (cT3N2M0) and underwent total cystectomy and ileum conduit construction after three courses of neoadjuvant chemotherapy. Eight months after the operation, the disease reoccurred in the pelvic lesion. He received pembrolizumab therapy but developed idiopathic thrombocytopenic purpura (ITP) immediately before the ninth course of administration; and, treatment was discontinued. Recovery of symptoms and normalization of blood test data were achieved 3.5months after starting steroid treatment. Reduction of recurrent disease has been maintained for 2 years.