Number Of Chemotherapy Cycles Research Articles

Problems of oxaliplatin-induced neuropathy in patients with colorectal cancer

Aim. To investigate the methods of early diagnosis of oxaliplatin-induced peripheral neuropathy (PN).Materials and methods. The study included 52 patients with diagnosis of metastatic colorectal cancer receiving 1st line polychemotherapy per the mFOLFOX6 scheme ± targeted therapy who prior to each cycle filled out the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ CIPN 20) and were subject to neurological examination using the Neuropathy Disability Scale (NDS).Results. The analysis included 28 patients who completed polychemotherapy: 16 (57,2 %) men and 12 (42,8 %) women, mean age 60.0 ± 10.0 years. Fridman’s two-way analysis of variance by ranks showed significant changes in the scores (sensory, motor, autonomic) of the EORTC QLQ CIPN 20 questionnaire with the increase in the number of chemotherapy cycles (р = 0.001). Significant increase in the sensory and motor scores was observed after the 3rd cycle, in the autonomic – after the 6th cycle. Significant increase in NDS score was observed starting at the 3rd cycle, and vibration sensitivity on the medial ankle or at the base of the 1st toe significantly decreased after the 1stcycle. Median number of cycles at which oxaliplatin dose was reduced or the drug was discontinued due to clinically significant symptoms of PN irrespective of questionnaire results and neurological examination was 6.Conclusion. According to the results of the study, the following conclusions were made: 1) sensory scale of the 3-part EORTC QLQ CIPN 20 questionnaire (9 questions of 20) or motor scale (7 questions of 20), vibration sensitivity can be considered as stand-alone informative tests; 2) in a large patient cohort, NDS score increase to 5, EORTC QLQ CIPN 20 sensory scale score increase to 12 and higher or decreased vibration sensitivity on the medial ankle or at the base of the 1st toe to 4.5 arbitrary units should be considered early manifestations of PN; 3) for a routine algorithm, it is acceptable to consider a combination of 9 questions of the sensory or 7 questions of the motor scales of the EORTC QLQ CIPN 20 questionnaire and evaluation of vibration sensitivity on the medial ankle or at the base of the 1st toe to decide on oxaliplatin dose reduction or measures for prevention of peripheral neuropathy symptom worsening.

The Association of Docetaxel Side Effects and Introduction of Subsequent Cabazitaxel for Castration-Resistant Prostate Cancer : A Clinical Study

The administration of cabazitaxel for patients with castration-resistant prostate cancer (CRPC) requires prior docetaxel therapy. Sequential chemotherapy may have to be discontinued due to docetaxelassociated side effects. This study investigated the relationship between treatment outcome of docetaxel and cabazitaxel and their associated side effects. We retrospectively analyzed 69 patients with CRPC who had been administered docetaxel withand without subsequent cabazitaxel at Toyonaka Municipal Hospital from October 2014 to June 2022. Twenty-eight patients (41%) discontinued docetaxel because of side effects, and the median number of docetaxel cycles at discontinuation was 2 (range : 1-11). Fourteen of these patients received no treatment following docetaxel. A comparison of the 28 patients who had discontinued docetaxel due to side effects with 41 patients who had not revealed a significant difference in the total numbers of chemotherapy cycles (2.5 vs 9 ; P＜0.001) and time to treatment failure (56 days vs 301 days ; P＝ 0.001), with a trend toward shorter overall survival from the start of docetaxel treatment (259 days vs 512 days ; P＝0.06). Multivariate analysis identified discontinuation of docetaxel due to side effects (OR＝0.07 ; P＜0.001) and lower hemoglobin (OR＝0.01 ; P＝0.001) as significant factors inhibiting the introduction of cabazitaxel. Reducing the side effects of docetaxel, including early drug switching, may allow more CRPC patients to be reached with cabazitaxel. Consequently, the resulting taxane-based chemotherapy may contribute to an additional survival advantage.

Resectability rate of pancreatic cancer after neoadjuvant therapy.

e16348 Background: Pancreatic Cancer is one of the leading causes of cancer death in Saudi Arabia. Surgery is the mainstay of treatment in resectable non-metastatic cases. Working on improving the resectability rate to achieve R0 resection is the standard of care. Methods: Unresectable cases of pancreatic adenocarcinoma seen from 2004 till 2018 in three hospitals in Saudi Arabia were reviewed to know the conversion rate from unresectable or borderline resectable to resectable after neoadjuvant chemotherapy and to explore the possible prognostic factors. The characteristics and outcomes of these patients were reviewed, with more attention on the known prognostic factors and their impact on the outcome. Notably, performance status, CA19-9, Neutrophil Lymphocyte Ration (NLR), and Platelet Lymphocyte Ratio (PLR). Overall response to neoadjuvant therapy, R0 resection, relapse free survival and overall survival were all reported. Results: Two hundred seventy-three captured cases of all types of pancreatic tumors from the tumor registry in the years between 2004 and 2018. 39 cases were unresectable or borderline resectable cases. The median age was 60 years (range:29-79), and 25 patients were males. 30 patients had an ECOG PS of 0-1and 6 had an ECOG PS of 2. The head of the pancreas was the primary tumor site in 31 patients and the body or tail was in 8 patients. 21 patients (54%) presented with weight loss ( > 5kg), and 21 patients (54%) presented with obstructive jaundice. Neoadjuvant chemotherapy protocols were FOLFORINOX (13 patients, 33%), Gemcitabine/Capecitabine (10 patients), single agent Gemcitabine (10 patients), and other regimens in 6 patients. The median number of chemotherapy cycles was 6 (range: 1-14). 17 patients had dose reduction. 6 patients had preoperative radiation. Response to chemotherapy: ORR: 36%, SD: 26% and PD: 38% .Surgery was done after neoadjuvant therapy in 12 patients (31%). Only 4 out 12 had confirmed R0. Median Overall Survival (MS) and Progression-Free survival (PFS) in all patients were 30 mo (95% CI: 17.75 - 42.56) and 8 mo (95% CI: 5.65 - 11.89) respectively. MS in the surgery and the non-surgery groups was 30 and 25 mo (p- value = 0.26) respectively. The median PFS in the surgery and the non-surgery groups was 19.6 and 5.8 mo (p- value = 0.008) respectively. Multivariate regression analysis done for the following variables: ECOG PS of 2, elevated CA 199, high NLR > 3, high PLR > 225, weight loss and results showed numerical difference of both MS and PFS with no statistical significance (Type 2 error). Conclusions: The conversion rate from unresectable or borderline resectable to resectable after neoadjuvant therapy is 31% which is consistent with the international data. There is PFS improvement in those who underwent surgery (19.6 mo vs. 5.8 mo) with statistical significance (p:0.008), and there is numerical improvement of MS (30 mo vs. 25 mo) that did not reach statistical significance.

Resectability rate of pancreatic cancer after neoadjuvant therapy.

e16348 Background: Pancreatic Cancer is one of the leading causes of cancer death in Saudi Arabia. Surgery is the mainstay of treatment in resectable non-metastatic cases. Working on improving the resectability rate to achieve R0 resection is the standard of care. Methods: Unresectable cases of pancreatic adenocarcinoma seen from 2004 till 2018 in three hospitals in Saudi Arabia were reviewed to know the conversion rate from unresectable or borderline resectable to resectable after neoadjuvant chemotherapy and to explore the possible prognostic factors. The characteristics and outcomes of these patients were reviewed, with more attention on the known prognostic factors and their impact on the outcome. Notably, performance status, CA19-9, Neutrophil Lymphocyte Ration (NLR), and Platelet Lymphocyte Ratio (PLR). Overall response to neoadjuvant therapy, R0 resection, relapse free survival and overall survival were all reported. Results: Two hundred seventy-three captured cases of all types of pancreatic tumors from the tumor registry in the years between 2004 and 2018. 39 cases were unresectable or borderline resectable cases. The median age was 60 years (range:29-79), and 25 patients were males. 30 patients had an ECOG PS of 0-1and 6 had an ECOG PS of 2. The head of the pancreas was the primary tumor site in 31 patients and the body or tail was in 8 patients. 21 patients (54%) presented with weight loss ( > 5kg), and 21 patients (54%) presented with obstructive jaundice. Neoadjuvant chemotherapy protocols were FOLFORINOX (13 patients, 33%), Gemcitabine/Capecitabine (10 patients), single agent Gemcitabine (10 patients), and other regimens in 6 patients. The median number of chemotherapy cycles was 6 (range: 1-14). 17 patients had dose reduction. 6 patients had preoperative radiation. Response to chemotherapy: ORR: 36%, SD: 26% and PD: 38% .Surgery was done after neoadjuvant therapy in 12 patients (31%). Only 4 out 12 had confirmed R0. Median Overall Survival (MS) and Progression-Free survival (PFS) in all patients were 30 mo (95% CI: 17.75 - 42.56) and 8 mo (95% CI: 5.65 - 11.89) respectively. MS in the surgery and the non-surgery groups was 30 and 25 mo (p- value = 0.26) respectively. The median PFS in the surgery and the non-surgery groups was 19.6 and 5.8 mo (p- value = 0.008) respectively. Multivariate regression analysis done for the following variables: ECOG PS of 2, elevated CA 199, high NLR > 3, high PLR > 225, weight loss and results showed numerical difference of both MS and PFS with no statistical significance (Type 2 error). Conclusions: The conversion rate from unresectable or borderline resectable to resectable after neoadjuvant therapy is 31% which is consistent with the international data. There is PFS improvement in those who underwent surgery (19.6 mo vs. 5.8 mo) with statistical significance (p:0.008), and there is numerical improvement of MS (30 mo vs. 25 mo) that did not reach statistical significance.

Analysis of sequential chemotherapy efficacy in ovarian epithelial carcinoma, fallopian tube carcinoma and primary peritoneal carcinoma

Objective: To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. Methods: A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel's Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups. Results: (1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups (Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions: Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.

HeredERA Breast Cancer: a phase III, randomized, open-label study evaluating the efficacy and safety of giredestrant plus the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with previously untreated HER2-positive, estrogen receptor-positive locally advanced or metastatic breast cancer

BackgroundHER2-positive, estrogen receptor-positive breast cancer (HER2+, ER+ BC) is a distinct disease subtype associated with inferior response to chemotherapy plus HER2-targeted therapy compared with HER2+, ER-negative BC. Bi-directional crosstalk leads to cooperation of the HER2 and ER pathways that may drive treatment resistance; thus, simultaneous co-targeting may optimize treatment impact and survival outcomes in patients with HER2+, ER+ BC.First-line (1L) treatment for patients with HER2+ metastatic BC (mBC) is pertuzumab, trastuzumab, and taxane chemotherapy. In clinical practice, dual HER2 blockade plus a fixed number of chemotherapy cycles are given as induction therapy to maximize tumor response, with subsequent HER2-targeted maintenance treatment given as a more tolerable regimen for long-term disease control. For patients whose tumors co-express ER, maintenance endocrine therapy (ET) can be added, but uptake varies due to lack of data from randomized clinical trials investigating the superiority of maintenance ET plus dual HER2 blockade versus dual HER2 blockade alone. Giredestrant, a novel oral selective ER antagonist and degrader, shows promising clinical activity and manageable safety across phase I–II trials of patients with ER+, HER2-negative BC, with therapeutic potential in those with HER2 co-expression.MethodsThis phase III, randomized, open-label, two-arm study aims to recruit 812 patients with HER2+, ER+ locally advanced (LA)/mBC into the induction phase (fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] plus a taxane) to enable 730 patients to be randomized 1:1 to the maintenance phase (giredestrant plus PH FDC SC or PH FDC SC [plus optional ET]), stratified by disease site (visceral versus non-visceral), type of LA/metastatic presentation (de novo versus recurrent), best overall response to induction therapy (partial/complete response versus stable disease), and intent to give ET (yes versus no). The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include overall survival, objective response rate, clinical benefit rate, duration of response, safety, and patient-reported outcomes.DiscussionheredERA BC will address whether giredestrant plus dual HER2 blockade is superior to dual HER2 blockade alone, to inform the use of this combination in clinical practice for maintenance 1L treatment of patients with HER2+, ER+ LA/mBC.Trial registrationClinicalTrials.gov, NCT05296798; registered on March 25, 2022. Protocol version 3.0 (November 18, 2022). Sponsor: F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124 4070, Basel, Switzerland.

Adapted EXTREME regimen in the first-line treatment of fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (ELAN-FIT): a multicentre, single-arm, phase 2 trial

A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC. This single-arm, phase 2 study was done at 22 centres in France. Eligible patients were aged 70 years or older and assessed as not frail (fit) using the ELAN Geriatric Evaluation (EGE) and had recurrent or metastatic HNSCC in the first-line setting that was not eligible for local therapy (surgery or radiotherapy), and an Eastern Cooperative Oncology Group performance status of 0-1. The adapted EXTREME regimen consisted of six cycles of fluorouracil 4000 mg/m2 on days 1-4, carboplatin with an area under the curve of 5 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on cycle 1-day 1, and 250 mg/m2 subsequently), all intravenously, with cycles starting every 21 days. In patients with disease control after two to six cycles, cetuximab 500 mg/m2 was continued once every 2 weeks as maintenance therapy until disease progression or unacceptable toxicity. Granulocyte colony-stimulating factor was systematically administered and erythropoietin was recommended during chemotherapy. The study was based on the two-stage Bryant and Day design, combining efficacy and toxicity endpoints. The primary efficacy endpoint was objective response rate at week 12 after the start of treatment, assessed by central review (with an unacceptable rate of ≤15%). The primary toxicity endpoint was morbidity, defined as grade 4-5 adverse events, or cutaneous rash (grade ≥3) that required cetuximab to be discontinued, during the chemotherapy phase, or a decrease in functional autonomy (Activities of Daily Living score decrease ≥2 points from baseline) at 1 month after the end of chemotherapy (with an unacceptable morbidity rate of >40%). Analysis of the coprimary endpoints, and of safety in the chemotherapy phase, was based on the per-protocol population, defined as eligible patients who received at least one cycle of the adapted EXTREME regimen. Safety in the maintenance phase was assessed in all patients who received at least one dose of cetuximab as maintenance therapy. The study is registered with ClinicalTrials.gov, NCT01864772, and is completed. Between Sept 27, 2013, and June 20, 2018, 85 patients were enrolled, of whom 78 were in the per-protocol population. 66 (85%) patients were male and 12 (15%) were female, and the median age was 75 years (IQR 72-79). The median number of chemotherapy cycles received was five (IQR 3-6). Objective response at week 12 was observed in 31 patients (40% [95% CI 30-51]) and morbidity events were observed in 24 patients (31% [22-42]). No fatal adverse events occurred. Four patients presented with a decrease in functional autonomy 1 month after the end of chemotherapy versus baseline. During chemotherapy, the most common grade 3-4 adverse events were haematological events (leukopenia [22 patients; 28%], neutropenia [20; 26%], thrombocytopenia [15; 19%], and anaemia [12; 15%]), oral mucositis (14; 18%), fatigue (11; 14%), rash acneiform (ten; 13%), and hypomagnesaemia (nine; 12%). Among 44 patients who received cetuximab during the maintenance phase, the most common grade 3-4 adverse events were hypomagnesaemia (six patients; 14%) and acneiform rash (six; 14%). The study met its primary objectives on objective response and morbidity, and showed overall survival to be as good as in younger patients treated with standard regimens, indicating that the adapted EXTREME regimen could be used in older patients with recurrent or metastatic HNSCC who are deemed fit with use of a geriatric evaluation tool adapted to patients with head and neck cancer, such as the EGE. French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer), Sandoz, GEFLUC, and GEMLUC. For the French translation of the abstract see Supplementary Materials section.

Safety and efficacy of neoadjuvant chemotherapy with paclitaxel, carboplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma.

As a substantial waiting time is usually required for radical surgery, safe and effective preoperative neoadjuvant chemotherapy (NAC) is desired for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). However, the significance of NAC in advanced HNSCC is still unclear. This study aimed to assess the safety and efficacy of NAC using the paclitaxel, carboplatin, and cetuximab (PCE) regimen. We retrospectively evaluated the background characteristics, incidence of adverse events, overall response rate (ORR), pathological response, recurrence-free survival (RFS), and overall survival (OS) in 26 patients. Patients receiving the PCE regimen were further divided into two groups based on the number of chemotherapy cycles (one cycle or more) and eligibility for cisplatin. Patients aged ≥ 75years and those with an estimated glomerular filtration rate (eGFR) < 60mL/min were classified as ineligible for cisplatin. The median age was 70 (27-81) years. The median eGFR at treatment initiation was 63.2 (41.1-89.7)mL/min. Fourteen (53.8%) patients were ineligible for cisplatin. Grade 3 or higher neutropenia was observed in 11 of 25 (42.3%) patients. No delay in or withdrawal from surgery was observed. The ORR was 65.4%. The 2-year RFS and OS were 61.5% and 76.7%, respectively. No significant differences in safety and efficacy between the number of chemotherapy cycles and cisplatin eligibility were observed. NAC using the PCE regimen for patients with locally advanced HNSCC, including cisplatin-ineligible patients, has acceptable toxicity and favorable efficacy.

Taste alteration and its relationship with nutritional status among cancer patients receiving chemotherapy, cross-sectional study

The aim of this study is to determine the prevalence of taste alterations (TAs) during chemotherapy and their association with nutritional status and malnutrition. In addition to the associated factors with TA, including sociodemographic health-related factors and clinical status, and to investigate coping strategies to manage TA. A multicenter cross-sectional design study was conducted on 120 cancer patients aged at least 18 who had been undergoing at least one round of chemotherapy. TAs were evaluated using the chemotherapy-induced taste alteration scale (CiTAS), the malnutrition universal screening tool (MUST) was used for nutritional screening, the antineoplastic side effects scale (ASES) was used for subjective assessment of chemotherapy side effects, and the Charlson comorbidity index (CCI) was used for comorbidity assessment. SPSS21 software was used to analyze the data, and the independent T-test and one-way ANOVA test were used to determine the association between TAs and a variety of related variables. The prevalence of TAs was 98.3%. Among participants, 48.3% were at low risk of malnutrition, 20% at medium risk, and 31.7% at high risk. Malnutrition risk was associated with taste disorders (p&lt;0.05). Patients’ age, gender, educational level, and physical status were associated with TAs (p&lt;0.05). Type of cancer, chemotherapy regimen, and number of chemotherapy cycles were also associated with TAs (p&lt;0.05). A variety of antineoplastic side effects were associated with TAs (p&lt;0.05), including nausea, vomiting, dry mouth, sore mouth and throat, excessive thirst, swallowing difficulty, appetite changes, weight loss, dizziness, lack of energy, disturbed sleep, anxiety, and difficulty concentrating. TAs were associated with an increased number of comorbidities, and individuals with diabetes, pulmonary diseases, and hypertension were associated with TAs (P&lt;0.05). Patients in this study rarely practice self-management strategies to cope with TAs. A high prevalence (98.3%) of TAs in cancer patients receiving chemotherapy was found, and it was linked to a variety of negative outcomes. Chemotherapy-induced TAs are an underestimated side effect that requires more attention from patients and health care providers.

J-AVENUE: A retrospective, real-world study evaluating patient characteristics and outcomes in patients with advanced urothelial carcinoma treated with avelumab first-line maintenance therapy in Japan.

The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.

Abstract PO4-20-05: An open label phase III randomized trial to evaluate the efficacy of Post-chemotherapy Axillary Conservation Surgery in breast cancer (PACS)

Abstract Background- Axillary lymph nodes (ALN) status is the most important prognostic factor in breast cancer. Traditionally, a complete axillary lymph node dissection (ALND) has been standard of care for those patients who have a positive node pre-chemotherapy. However, lately axillary conservation is paving its way in the post-chemotherapy setting as well to avoid significant morbidity of ALND. Most sentinel node biopsy studies have failed to achieve the desired false negative rate(FNR). (Boughey JC et al, JAMA. 2013 Oct; Kuehn T et al, Lancet Oncol. 2013; Boileau JF et al, J Clin Oncol. 2015 Jan).We previously reported a low FNR of low axillary sampling (LAS) in the post-chemotherapy setting. (Parmar et al, JCO-GO, 2021) We are conducting a phase III, randomised controlled trial of LAS versus complete ALND in post-chemotherapy negative (ypN0) axilla. Aims and objectives- The primary objective is to assess the non-inferiority of LAS in patients who are rendered ypN0 by pre-operative chemotherapy with disease-free survival as primary end point. The secondary objectives are comparing the morbidity of ALND (lymphedema, paraesthesia, and shoulder dysfunction) in the LAS and ALND arms, and to evaluate the impact on overall survival, local, regional, and distant recurrence free survival and quality of life. Trial design- This is a prospective, open label, randomised, phase III trial where histologically proven, non-metastatic, cT1-4,N0-2 breast cancer patients who are rendered ycN0 after pre-operative systemic chemotherapy are being accrued. Patients with prechemo N3 disease, inflammatory breast cancer, recurrent disease, pregnancy associated breast cancer are being excluded from the study. The chemotherapy regimens and surgical assessment is as per standard institutional protocols. After obtaining informed consent, patients undergo LAS during surgery and lymph nodes(LN) are sent for frozen section analysis. If any LN is found to be involved, a complete ALND is carried out. If the staging procedure is negative, then patients are randomised into 2 groups- observation v/s complete ALND. Stratification factors are T stage, N stage, Hormone receptor status, Her2 receptor status and number of chemotherapy cycles taken. Morbidity assessment is done with- Constans shoulder score, arm volumetry, paraesthesia assessment, and a QOL questionnaire- Self-reported Breast cancer Lymphedema Symptom Experience Index (BCLSEI). A baseline assessment pre-surgery is followed by 6 monthly morbidity assessments and regular oncologically relevant follow-up up to 5 years. A two-sided log-rank test with an overall sample size of 2316 with a 10% dropout rate (1158 in ALND and 1158 in LAS group) achieves 80% power at a 0.05 significance level to detect a hazard ratio of 1.16 (upper limit of non-inferiority) when the proportion surviving in the control group is 0.71. An interim analysis will be carried out at 25% events and conditional power will be calculated. If the conditional power is below 20%, then the study will be discontinued for futility. The study has been approved by Institutional Ethics Committee (CTRI/2022/07/044461) Expected Study and Results- We started accrual in February 2023 and have screened 63 and randomized 45 patients until now. Ours is a first large randomised prospective study in the post-chemotherapy axillary management setting which will help us understand the efficacy of axillary conservation surgery in patients who are node negative post neoadjuvant chemotherapy. In future, lesser morbid procedures than LAS like targeted axillary dissection can be tested in the same trial. However, LAS as a technique of axillary conservation suits resource constraints and high volume setting such as ours. Citation Format: Shalaka Joshi, Jessicka Shah, Pallavi Daphale, Rohini Hawaldar, Anuradha Daptardar, Ayushi Sahay, Tanuja Shet, Palak Popat, Tabassum Wadasadawala, Nita Nair, Vani Parmar, Bipin Bandre, Shabina Siddique, Vaibhav Vanmali, Sudeep Gupta, Rajendra Badwe. An open label phase III randomized trial to evaluate the efficacy of Post-chemotherapy Axillary Conservation Surgery in breast cancer (PACS) [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 PO4-20-05.

Evaluation of Antiemetic Consistency in Chemotherapy-Induced Nausea and Vomiting Among NHL Patients in Sana'a, Yemen.

Chemotherapy-induced nausea and vomiting (CINV) is a prevalent and distressing adverse effect that can negatively affect a patient's quality of life and treatment adherence. This study aimed to evaluate the consistency of antiemetic use with standard guidelines and to examine the factors influencing it. This cross-sectional study was conducted at the National Oncology Center (NOC) of Al-Jomhouri Teaching Hospital, Sana'a, Yemen, from November 2022 to September 2023. Demographic data, chemotherapy and antiemetic regimens, dosages, and patient-related risk factors were collected via direct interviews, medical records, and treatment charts. This study evaluated the consistency of antiemetic practices among non-Hodgkin's Lymphoma (NHL) patients using the National Comprehensive Cancer Network (NCCN) guidelines. The chi-squared test and regression were used to determine the factors associated with guideline consistency. A total of 251 patients with NHL were recruited for the study; 57.4% were male and 60.6% were aged between 18-49. Most of the patients received moderately emetogenic chemotherapy (81.3%). The overall consistency with the NCCN guidelines was only 23.9%, with antiemetic drug selection and dosage reported inconsistently in 62.9% and 16.7% of patients, respectively. Furthermore, 62.5% of the patients received an under-prescribed antiemetic prophylactic regimen. Treatment duration, number of chemotherapy cycles, emetogenic risk potential, and overall patient risk, as well as age, sex, and marital status, were significantly associated with guideline inconsistency (p < 0.05). This study revealed a notable gap in the consistency of antiemetic prescriptions among patients with NHL. Inappropriate drug selection, dosing, and under-prescription are common problems. Patient regimen risk factors significantly influenced the consistency of the National Comprehensive Cancer Network guidelines. Personalized approaches are essential to enhance adherence to guidelines and improve antiemetic strategies.

Factors associated with perceived cognitive function in breast cancer patients treated with chemotherapy: A multicenter cross-sectional study

PurposeThis study aimed to investigate the factors associated with perceived cognitive function among breast cancer patients treated with chemotherapy in China. MethodsThe study was a multicenter cross-sectional design. Data were collected from 10 public hospitals in China between April 2022 and February 2023. A total of 741 participants completed questionnaires assessing sociodemographic and medical characteristics, perceived cognitive function, sleep quality, fatigue, anxiety, and depression. Hierarchical multiple regression analysis was used to assess the determinants of cognitive function. ResultsThe hierarchical multiple regression model accounted for 31.5% of variation in perceived cognitive function (sociodemographic 4.5%; medical 6.6%; exercise frequency 6.6%; sleep quality 2.1%; fatigue 2.8%; anxiety combined with depression 9.0%). Education level, chemotherapy type, number of chemotherapy cycles, and cyclophosphamide drug use were significant predisposing factors of perceived cognitive function (p < 0.001). Exercising ≥3 times/week (p < 0.001) was a significant factor positively influencing perceived cognitive function, meanwhile, anxiety (p < 0.001) and depression (p < 0 0.001) were negative factors. ConclusionOur findings suggest that patients with low education levels, postoperative chemotherapy, cyclophosphamide treatment, and a greater number of chemotherapy cycles need more assessment. Sedentary patients, those who have never exercised, and those with anxiety or depression all showed greater cognitive decline. By identifying susceptible populations, encouraging regular exercise, and addressing anxiety and depression, healthcare professionals can contribute significantly to prevent patients’ cognitive decline throughout chemotherapy.

MRI-guided optimisation of neoadjuvant chemotherapy duration in stage II–III HER2-positive breast cancer (TRAIN-3): a multicentre, single-arm, phase 2 study

Patients with stage II-III HER2-positive breast cancer have good outcomes with the combination of neoadjuvant chemotherapy and HER2-targeted agents. Although increasing the number of chemotherapy cycles improves pathological complete response rates, early complete responses are common. We investigated whether the duration of chemotherapy could be tailored on the basis of radiological response. TRAIN-3 is a single-arm, phase 2 study in 43 hospitals in the Netherlands. Patients with stage II-III HER2-positive breast cancer aged 18 years or older and a WHO performance status of 0 or 1 were enrolled. Patients received neoadjuvant chemotherapy consisting of paclitaxel (80 mg/m2 of body surface area on day 1 and 8 of each 21 day cycle), trastuzumab (loading dose on day 1 of cycle 1 of 8 mg/kg bodyweight, and then 6 mg/kg on day 1 on all subsequent cycles), and carboplatin (area under the concentration time curve 6 mg/mL per min on day 1 of each 3 week cycle) and pertuzumab (loading dose on day 1 of cycle 1 of 840 mg, and then 420 mg on day 1 of each subsequent cycle), all given intravenously. The response was monitored by breast MRI every three cycles and lymph node biopsy. Patients underwent surgery when a complete radiological response was observed or after a maximum of nine cycles of treatment. The primary endpoint was event-free survival at 3 years; however, follow-up for the primary endpoint is ongoing. Here, we present the radiological and pathological response rates (secondary endpoints) of all patients who underwent surgery and the toxicity data for all patients who received at least one cycle of treatment. Analyses were done in hormone receptor-positive and hormone receptor-negative patients separately. This trial is registered with ClinicalTrials.gov, number NCT03820063, recruitment is closed, and the follow-up for the primary endpoint is ongoing. Between April 1, 2019, and May 12, 2021, 235 patients with hormone receptor-negative cancer and 232 with hormone receptor-positive cancer were enrolled. Median follow-up was 26·4 months (IQR 22·9-32·9) for patients who were hormone receptor-negative and 31·6 months (25·6-35·7) for patients who were hormone receptor-positive. Overall, the median age was 51 years (IQR 43-59). In 233 patients with hormone receptor-negative tumours, radiological complete response was seen in 84 (36%; 95% CI 30-43) patients after one to three cycles, 140 (60%; 53-66) patients after one to six cycles, and 169 (73%; 66-78) patients after one to nine cycles. In 232 patients with hormone receptor-positive tumours, radiological complete response was seen in 68 (29%; 24-36) patients after one to three cycles, 118 (51%; 44-57) patients after one to six cycles, and 138 (59%; 53-66) patients after one to nine cycles. Among patients with a radiological complete response after one to nine cycles, a pathological complete response was seen in 147 (87%; 95% CI 81-92) of 169 patients with hormone receptor-negative tumours and was seen in 73 (53%; 44-61) of 138 patients with hormone receptor-positive tumours. The most common grade 3-4 adverse events were neutropenia (175 [37%] of 467), anaemia (75 [16%]), and diarrhoea (57 [12%]). No treatment-related deaths were reported. In our study, a third of patients with stage II-III hormone receptor-negative and HER2-positive breast cancer had a complete pathological response after only three cycles of neoadjuvant systemic therapy. A complete response on breast MRI could help identify early complete responders in patients who had hormone receptor negative tumours. An imaging-based strategy might limit the duration of chemotherapy in these patients, reduce side-effects, and maintain quality of life if confirmed by the analysis of the 3-year event-free survival primary endpoint. Better monitoring tools are needed for patients with hormone receptor-positive and HER2-positive breast cancer. Roche Netherlands.

Six versus four or five cycles of first-line etoposide and platinum-based chemotherapy combined with thoracic radiotherapy in patients with limited-stage small-cell lung cancer: A propensity score-matched analysis of a prospective randomized trial.

The recommended treatment for limited-stage small-cell lung cancer (LS-SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4-6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS-SCLC who received either 6 cycles or 4-5 cycles of EP chemotherapy combined with TRT. In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS-SCLC patients who received 4-6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4-5 cycles. To assess overall survival (OS) and progression-free survival (PFS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). Among the 265 LS-SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4-5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4-5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6-53.1 months) vs. 22.7 months (95% CI, 20.8-29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7-30.5 months) vs. 12.0 months (95% CI, 9.8-14.2 months), respectively, p = 0.006]. The two-year and five-year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4-5 cycles group, respectively. Patients diagnosed with LS-SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4-5 cycles.

Risk factors and the nomogram model for malnutrition in patients with nasopharyngeal carcinoma.

For patients with nasopharyngeal carcinoma (NPC), the incidence of malnutrition is quite high, and malnutrition has severe effects on NPC patients. However, there is currently no recognized gold standard or specific nutritional assessment tool available to assess malnutrition in NPC patients. Our objective was to develop and verify a new nomogram model for NPC patients. Data were collected from NPC patients. To evaluate risk factors for malnutrition, univariate and multivariate logistic regression analyses were used. Based on the risk factors, a new nomogram model was developed. The efficacy of the model was evaluated and validated. Logistic regression analysis showed that age ≥ 65years, the number of chemotherapy cycles completed ≥ 1, a high total radiation dose received, low body mass index (BMI), low albumin, and low chloride were the risk factors. The assessment effect of the new model was good by evaluation and validation; it can be used as an assessment tool for malnutrition in NPC patients. Age ≥ 65years, completing ≥ 1 chemotherapy cycles, a high total radiation dose received, low BMI, low albumin, and low chloride levels are risk factors for malnutrition in NPC patients. The assessment effect of the new model, developed based on these risk factors, is good, and it can be used as an assessment tool for malnutrition in NPC patients.

Significance of HIV status in cervical cancer patients receiving curative chemoradiation therapy, definitive radiation alone, or palliative radiation in Botswana.

Cervical cancer associated with human papillomavirus has the highest cancer incidence and mortality for women in Botswana because of a high HIV prevalence and limited screening. This study investigates the significance of HIV on the overall survival (OS) of patients with locally advanced cervical cancer by various treatment categories (curative chemoradiation, definitive radiation [RT] alone, or palliative RT alone). This study included patients diagnosed with cervical cancer between 2013 and 2020, prospectively enrolled in the Botswana Prospective Cancer Cohort. OS based on HIV status and completion of planned treatment regimen was estimated by the Kaplan-Meier method. Comparisons of 2-year OS by HIV status was performed by the log-rank test, univariate and multivariable Cox analyses adjusting for cancer stage, RT dose, number of chemotherapy cycles, and baseline hemoglobin levels. Of 1131 patients diagnosed with stage IB-IVB cervical cancer, 69.8% were women living with HIV (n=789). For patients receiving curative chemoradiation, HIV status was not significantly associated with OS in unadjusted (p=.987) and adjusted (p=.578) analyses. For RT only treatment and definitive (high-dose) RT alone, HIV status was significantly associated with OS in unadjusted analysis (HR=1.77, p=.002; HR=1.95, p=.014), but not in adjusted analysis (p=.227, p=.73). For patients receiving palliative (low-dose) RT, HIV status was not associated with OS in unadjusted (p=.835) or adjusted analysis (p=.359). In Botswana, a resource-limited setting, HIV status had no significant effect on 2-year OS in patients with cervical cancer with well-managed HIV receiving chemoradiation, RT alone, or palliative RT. This demonstrates that patients living with HIV receiving antiretroviral treatment can receive clinically appropriate treatment with no evidence that HIV may lead to poorer outcomes.

Apparent diffusion coefficient values predict response to brachytherapy in bulky cervical cancer

BackgroundDiffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer.MethodsClinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden’s J statistic was used to identify a threshold value.ResultsAmong 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10− 3 mm2/s were 5.33 (95% CI, 1.35–24.4) times more likely to achieve CMR.ConclusionsClinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.

Catastrophic Health Expenditure and Associated Factors Among Hospitalized Cancer Patients in Addis Ababa, Ethiopia.

Out-of-pocket (OOP) health expenditures for cancer care expose households to unanticipated economic consequences. When the available health services are mainly dependent on OOP expenditure, the household faces catastrophic health expenditure (CHE). This study aimed to estimate the incidence and intensity of CHE in hospitalized cancer patients and identify coping strategies and associated factors. Hospital-based cross-sectional study design was conducted on 305 cancer inpatients in Addis Ababa between November 2021 and February 2022. All patients with cancer who were hospitalized during the data collection period were included in the study. The incidence of CHE was estimated at the 40% threshold of households' non-food expenditure and the intensity of CHE was captured based on the amount by which household expenditure exceeded the threshold and mean positive overshoot, the mean level by which CHE exceeds the threshold used. Multivariate logistic regression was used to assess the relationship between CHE levels and the independent variables. The incidence of CHE at the 40% threshold of households' non-food expenditure was 77.7%, while the O and MPO were 36.2% and 46.6%, respectively. CHE for cancer care was significantly associated with patient residence, increased number of chemotherapy cycles, increased duration of hospital admission, lack of insurance enrolment, and lower-income quintiles. Saving and selling assets were identified as the primary coping mechanisms. The incidence and intensity of CHE among inpatients with cancer were high and which could lead to impoverishment of households. Improved quality and coverage of health insurance and decentralizing cancer care to regions standards similar to Addis Ababa will save households from incurring CHE.

Neoadjuvant Chemotherapy in Locally Advanced Sinonasal Teratocarcinosarcoma a Rare Malignancy: An Audit From an Academic Tertiary Care Centre in India

AimsSinonasal teratocarcinosarcomas (SNTCS) are rare sinonasal malignancies, the incidence of which is less than 1% of all tumors. There is limited data available on SNTCS's, often as case reports and small case series. The management of SNTCS is complicated because of its location, locally aggressive biology, difficulty in achieving complete resection, and limited data on chemotherapy in these malignancies. This audit was performed to understand the role of neoadjuvant chemotherapy (NACT) in SNTCS's, its ability to downstage the disease, achieve complete resection, and impact on long-term survival outcomes. MethodsThis was a retrospective analysis of a prospectively maintained database approved by the Institutional Ethics Committee (IEC). The baseline characteristics, the extent of tumor, Kadish stage, NACT regimen, and adverse events were extracted from the Electronic Medical Records and the patient's case file. Patients with baseline extensive/inoperable disease were referred for NACT from the multidisciplinary joint clinic followed by response assessment (RECIST v1.1). Patients underwent skull-base surgery if respectable post-completion of NACT, however, if deemed unresectable were treated with non-surgical modalities or palliative therapies. ResultsThe data of 27 patients were evaluated from the year 2015–2022. The median age was 42 years (IQR:30–56) and 85.2% (n = 23) were males. The ECOG-PS was 0–1 in 88.8% (n = 24) patients. All 27 patients received NACT in view of extensive disease at presentation. 74.1% (n = 20) patients received Cisplatin-Etoposide and 25.9% (n = 7) received other chemotherapy regimens. The median number of chemotherapy cycles was 2(IQR:2–3). 96.3% patients (n = 26) completed the planned NACT cycles. 70.4% (n = 19) patients achieved a partial response in post-NACT imaging. 77.8% (n = 18) underwent surgery, 18.5% (n = 5) received CTRT, and 7.4% (n = 2) received definitive-RT alone. The median PFS and OS of the cohort was 19months (95%CI:12.0–25.6) and 23months (95%CI:5.94–40.06) respectively. ConclusionNACT is safe, feasible, and effective with significant response rates, leading to effective downstaging, resectability and improved survival in patients with locally advanced SNTCS's.