Received Combination Chemotherapy Research Articles

A prospective phase 2 study of combination epigenetic therapy against relapsed/refractory peripheral T cell lymphoma

Peripheral Tcell lymphomas (PTCLs) are prototypical epigenetic malignancies with invariably poor prognoses. Novel and effective therapeutic strategies are needed to improve clinical outcomes, particularly in relapsed/refractory patients. We conducted a multicenter phase 2 study to evaluate the therapeutic efficacy of azacitidine and chidamide, alone or in combination with gemcitabine and oxaliplatin (GemOx), in patients with relapsed/refractory PTCLs (registration number: ChiCTR2000037232). The primary endpoint was the best overall response rate. As of May 1st, 2024, thirty patients were evaluable for efficacy and toxicity. The best overall response rate was 53.3%, meeting its primary endpoint. Among the patients with angioimmunoblastic Tcell lymphoma (AITL; N= 19), a numerically higher response rate was observed, regardless of whether chemotherapy was combined, compared to patients with non-AITL. After a median follow-up of 36.6months, median progression-free survival and overall survival were 7.1 and 8.7months, respectively. Patients with AITL who received combination chemotherapy (N= 12) achieved the most promising response rates (overall response rate, 91.7%; complete remission rate, 66.7%) and survival outcomes (median progression-free survival, 17.2months; median overall survival, 38.8months). The most common grade 3-4 toxicities were neutropenia (40.0%) and thrombocytopenia (30.0%). The combination of epigenetic therapy with GemOx was well tolerated and highly effective in patients with relapsed/refractory PTCLs. Patients with AITL, in particular, may benefit more from this combination treatment and should be the focus of future studies. This work was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).

Electronic clinical quality measure (eCQM) concordance and quality care disparities among patients with breast cancer (BC).

e23237 Background: BC mortality is decreasing steadily, yet disparities in treatment and outcomes persist. eCQMs are metrics specified in a standard electronic format using data from electronic health records (EHR) and other systems to measure care quality. CancerLinQ is a health technology platform aggregating EHR data from ~7M patients (pts) seen in US oncology practices and cancer centers. This analysis assesses odds of non-concordance with 4 BC-specific eCQMs in CancerLinQ. Methods: Pts actively treated for BC in 2021 in CancerLinQ data were included in this study. The following four practice-level eCQMs were assessed as proportions of BC pts who: eCQM1 – Undergo HER2 testing eCQM2 – Are < age 70 with early-stage, hormone receptor (HR) negative BC who receive combination chemotherapy < 4 months of dx eCQM3 – Have early-stage, HER2+ BC and receive trastuzumab eCQM4 – Have early-stage, HR+ BC and receive tamoxifen or an aromatase inhibitor (AI) < 1-year of dx Ethnicity, race, age at dx, pt/practice rural status, and practice type were assessed as covariates. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were calculated for associations among study variables and receipt of guideline non-concordant care. Results: aORs (95% CI) of pt characteristics were compared to reference groups - non-Hispanic, white, age at dx 60-69, married, urban: eCQM1 (N = 21296): For unknown ethnicity, aOR (95% CI) = 1.5 (1.3 1.6); unknown race = 1.3 (1.2, 1.5); age 70-79 = 1.1 (1.0, 1.2), age 80-89 = 1.4 (1.2, 1.5), age > 90 = 1.5 (1.1, 2.2); formerly married/partnered = 1.2 (1.1, 1.3), thus having greater odds of non-concordance. Age 40-49, aOR (95% CI) = 0.9 (0.8, 0.986), had lower odds of non-concordance. eCQM2 (N = 1259): For unknown ethnicity, aOR (95% CI) = 1.9 (1.2, 3.1); Asian = 2.9 (1.7, 4.9) or other race = 2.3 (1.2, 4.1); and formerly married/partnered = 1.7 (1.2, 2.6), thus having greater odds of non-concordance. Pts age < 40 = 0.6 (0.3, 0.9) had lower odds of non-concordance. eCQM3 (N = 1341): Age > 80, aOR (95% CI) = 3.8 (1.5, 9.1), had greater odds of non-concordance. eCQM4 (N = 5063): For age < 40, aOR (95% CI) = 2.9 (2.1, 4.1), age 40-49 = 1.6 (1.2, 2.0), and age 50-59 = 1.5 (1.2, 1.9); and formerly married/partnered = 1.3 (1.1, 1.7), thus having greater odds of non-concordance. Conclusions: As expected, pts < 40 had greater odds of receiving chemotherapy and pts > 80 had lower odds of receiving trastuzumab, possibly due to cardiotoxicity concerns. Although all women with early-stage HR+ BC are potential tamoxifen/AI candidates, pts < 60 with early-stage HR+ BC had greater odds of not receiving tamoxifen/AI compared to those age 60-69. Additionally, divorced, separated, or widowed pts had greater odds of non-concordant care in 3 of 4 of eCQMs assessed. Our findings demonstrate the ability of eCQMs to identify clinical subgroups more likely to receive non-concordant care who may be eligible for targeted interventions.

Circulating tumor cells enumeration and characterization in patients with lung cancer treated with immunotherapy.

e15030 Background: Programmed death-ligand 1 (PD-L1) is a predictive biomarker for immunotherapy in the treatment of non-small cell lung cancer (NSCLC). Assessing PD-L1 expression from the tumor specimen can be challenging because of tissue accessibility, heterogeneity, and dynamic changes in PD-L1 expression that may impact the status of PD-L1 during disease evolution and treatment. Hence, assessing PD-L1 status from archival tumor might not reflect its actual state on the tumor and having a real-time assessment of its expression with the use of non-invasive techniques such circulating tumor cells (CTCs) is useful. Methods: We conducted a single centre prospective study to detect CTCs in the blood of patients with stage III-IV NSCLC treated with immunotherapy using the standard CellSearch technology for CTC enumeration and the Epic Sciences technology for CTCs enumeration and assessment of PD-L1 protein expression on CTCs. CTCs were detected at baseline before treatment initiation and after 2 cycles of treatment. Study endpoints included CTCs detection and concordance between the 2 technologies, PD-L1 expression assessment on CTCs with the Epic Sciences technology, and concordance with tissue-based expression. Comparisons were made using Pearson correlation coefficient (PCC) and intraclass correlation coefficient (ICC) for count data and percentage of perfect agreement. Results: Between 2019 and 2022, 48 patients treated with immunotherapy were enrolled in the study. The mean ± standard deviation (SD) age was 66.8 ± 10.3 years, 63% were females, 42% received combination chemotherapy and immunotherapy, and 44% had adenocarcinoma histology. The tissue PD-L1 expression was high (≥50%), intermediate (1-49%), and low (<1%) in 36%, 31% and 33% of patients respectively. The mean ± SD baseline CTCs count per 7.5ml was 1.97 ± 4 with CellSearch and 1.38 ± 2.72 per ml with Epic Sciences. After 2 treatment cycles, 22% and 41% of patients had an increase in their CTCs count with CellSearch and Epic Sciences, respectively and 30% and 29% had a decrease in their CTCs. The PCC and ICC for baseline CTCs detected by CellSearch and Epic Sciences were 0.72 and 0.61, respectively and for CTCs detected after 2 cycles of treatment by the 2 technologies were -0.16 and 0.45 respectively. One patient had PD-L1 expression on their CTCs with the Epic Sciences technology and there was no association between the PD-L1 expression on CTCs and on matched tissue samples. Conclusions: This study showed a moderate to strong correlation between the 2 technologies for baseline CTCs detection and moderate to poor correlation for CTCs detection after 2 cycles of therapy. No association was found between CTCs and tissue PD-L1 expression. Future work needs to further investigate the role of PD-L1 expression on CTCs.

Early tumor response in first‐line palbociclib plus AI in Chinese women with HR+/HER2- advanced breast cancer: Primary analysis of a multicenter, prospective real-world study.

e13078 Background: The CDK4/6 inhibitors (CDK4/6i) and aromatase inhibitors (AIs) regimen is the first-line standard for HR+/HER2- advanced breast cancer. Despite this, high-risk patients often receive combination chemotherapy for quicker disease control, a practice supported by anecdotal evidence of the efficacy of the CDK4/6i and AI combination but lacking rigorous research validation. Early tumor shrinkage (ETS), a prognostic marker in colorectal cancer, remains undefined in HR+ breast cancer. This study (NCT04858997) aims to investigate the early effectiveness of the CDK4/6i and AI combination through ETS, addressing a significant gap in the literature. Methods: This study enrolled HR+/HER2- advanced breast cancer patients diagnosed between April 2021 and October 2023, who were treatment-naïve for their advanced disease and consented to palbociclib and AI therapy. Participants underwent CT scans to evaluate treatment response at baseline, week 4, week 12, and every 12 weeks thereafter. The study primarily investigated ETS, defined herein as a ≥10% reduction in the sum of diameters of target lesions by week 4. Secondary endpoints encompassed TTR, ORR, and PFS. Results: The study enrolled 30 patients with a median age of 55 years (range 29-76); 30% were premenopausal, and 40% presented with ≥3 metastatic sites. Visceral metastases were observed in 53.3% of the cohort (N=16). ETS was achieved in 73.3% of patients at the first assessment 4 weeks post-treatment initiation, with 68.8% in patients with visceral metastases and 78.8% in those without. The mTTR=3 months, differing between patients with visceral metastases (6 months) and those without (3 months). The overall response rate (ORR) was 63.3%. The ETS outcomes predict the best response in patients, with 77.3% reaching ETS eventually achieving partial or complete response (PR/CR), compared to only 25% of those not reaching ETS. Conclusions: This study validates the CDK4/6i and AI combination's early effectiveness in HR+/HER2- advanced breast cancer, showing that 4-week treatment responses predict best of response outcomes. Achieving ETS is closely linked to a higher likelihood of therapeutic success, underscoring its value as a prognostic marker for informed therapy choices.

Safety and efficacy of PEG-rhG-CSF as primary prophylaxis against neutropenia induced by combination chemotherapy regimens involving oral chemotherapy agents in gastrointestinal cancer patients: A prospective, exploratory, non-randomized controlled study.

e24107 Background: The safety and efficacy of PEGylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for prevention of chemotherapy-induced neutropenia (CIN) in patients undergoing oral chemotherapy remain unclear. This study investigated the safety and efficacy of PEG-rhG-CSF as primary prophylaxis against CIN in gastrointestinal (GI) cancer patients receiving combination chemotherapy regimens involving oral chemotherapy agents. Methods: This is a prospective, single-center, open-label, exploratory, non-randomized controlled study. GI cancer patients receiving two consecutive cycles of IV oxaliplatin (150mg/m2 on day 1) combined with oral capecitabine 1000mg/m2 or tegafur gimeracil oteracil potassium capsule 40-60mg twice daily on days 1-14 every 3 weeks. PEG-rhG-CSF (6mg) was administered subcutaneously 24 hours post-oxaliplatin treatment in the PEG-rhG-CSF group, while the control group did not receive it. The primary endpoint was safety, and secondary endpoints included CIN incidence and neutropenic complications. The study was registered with the Chinese Clinical Trial Registry (registration number ChiCTR2100054854). Results: Between March 2022 and January 2023, a total of 49 patients was screened, and 43 patients completed the treatment (26 in PEG-rhG-CSF group and 17 in control group). The average age was 61.4 years, with 90.7% males and 83.7% having gastric cancer. Baseline characteristics were similar between the two groups. The overall adverse events (AE) did not differ statistically (88.5% vs. 88.2%, p = 1.000), with grade £2 fatigue and nausea being the most common AEs. Grade 3 platelet reduction showed no significant difference between the two groups (7.69% vs. 17.65%, p = 0.432). Four cases of bone pain (15.4%) and five cases of injection site reactions below grade 3 (19.2%) were observed in the PEG-rhG-CSF group. Grade ≥2 CIN was significantly lower in the PEG-rhG-CSF group (3.84% vs. 58.82%, p < 0.001). One case in the PEG-rhG-CSF group required antibiotic treatment due to febrile neutropenia. Regarding neutropenic complications, the PEG-rhG-CSF group exhibited lower proportion of chemotherapy delay (3.85% vs. 35.29%, p < 0.001) and dose reduction (1.92% vs. 23.53%, p = 0.002). Rescue treatment with rhG-CSF for grade 3/4 CIN was significantly less frequent in the PEG-rhG-CSF group (1.92% vs. 23.53%, p = 0.002). Conclusions: Primary prophylaxis with PEG-rhG-CSF in GI cancer patients undergoing oral capecitabine/tegafur gimeracil oteracil potassium may be safe, without an increased chemotherapy-related AEs, and is associated with a reduced grade ≥2 CIN. Clinical trial information: ChiCTR2100054854.

Effect of sustained measurable residue disease negativity and post-remission treatment selection on the prognosis of acute lymphoblastic leukemia in adults.

To explore the effects of monitoring measurable residual disease and post-remission treatment selection on the clinical outcomes of B-cell acute lymphoblastic leukemia (B-ALL) in adults. Between September 2010 and January 2022, adult patients with B-ALL who received combination chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (allo-HSCT), were included in the retrospective study, which was approved by the Ethics Committee and the observation of Declaration of Helsinki conditions. One hundred and forty-three B-ALL patients achieved complete remission (CR) were included in the study, of whom 94 patients (65.7%) received allo-HSCT in first complete remission (CR1). Multivariate analysis showed that the most powerful factors affecting OS were transplantation (hazard ratio [HR] = 0.540, p = 0.037) and sustained measurable residue disease (MRD) negativity (HR = 0.508, p = 0.037). The subgroup analysis showed that the prognosis of the allo-HSCT group was better than that of the chemotherapy group, regardless of whether MRD was negative or positive after two courses of consolidation therapy. After consolidation therapy, the prognosis of patients with positive MRD remained significantly better in the allo-HSCT group than in the chemotherapy group. However, no significant difference was observed in the prognosis between the allo-HSCT and chemotherapy groups with negative MRD after consolidation therapy. B-ALL patients who achieve sustained MRD negativity during consolidation therapy have excellent long-term outcomes even without allo-HSCT. Allo-HSCT is associated with a significant benefit in terms of OS and DFS for patients who were with positive MRD during consolidation therapy.

Long-Term Survival Rates and Treatment Trends of Burkitt Lymphoma in Patients with HIV-A National Cancer Database (NCDB) Study.

Burkitt lymphoma (BL) accounts for 10-35% of AIDS-defining lymphoma in people with HIV (PWH). Previous research consisting of smaller cohorts has shown decreased survival for HIV-associated BL. This study aims to compare overall mortality in BL patients with and without HIV, while investigating impact of treatment modalities in HIV-associated BL. Using the 2004-2019 NCDB, we identified 4312 patients with stage 3 or 4 BL who had a known HIV status and received either chemotherapy alone or chemotherapy and immunotherapy. Time to death was evaluated using Kaplan-Meier survival estimates. Risk of death was evaluated using an extended multivariable Cox model adjusted for multiple factors and with a Heaviside function for HIV status by time period (0-3 month vs. 3-60 month). Of the 4312 patients included, 1514 (35%) had HIV. For months 0-3 from time of diagnosis, HIV status was not associated with a statistically significant increase in risk of death (HR = 1.04, 95% CI: 0.86, 1.26, p = 0.6648). From month 3to 60, positive HIV status was associated with a 55% increase in risk of death compared to those without HIV (95% CI: 1.38, 1.75, p < 0.0001). Further, this difference in hazard rates (0-3 vs. 3-60) was statistically significant (HR = 1.49, 95% CI: 1.22-1.82, p < 0.001). There is an increased mortality rate from months 3 to 60 in BL patients with HIV compared to patients without HIV. Additionally, risk of death in the first 3 months is significantly decreased by 45% in patients with HIV treated with combination chemotherapy and immunotherapy compared to patients without HIV receiving combination chemotherapy and immunotherapy, providing valuable clinical insight into treatment decision making in the care of HIV-associated BL.

Safety of pegfilgrastim in patients with metastatic germ-cell tumor receiving combination chemotherapy containing bleomycin.

Safety of pegfilgrastim in patients with metastatic germ-cell tumor receiving combination chemotherapy containing bleomycin.

Analysis of Risk Factors for Febrile Neutropenia in Patients with Small-Cell Lung Cancer Receiving Carboplatin Plus Etoposide Therapy

Introduction: Febrile neutropenia (FN) is an oncologic emergency requiring immediate empiric antibiotic therapy. Although carboplatin plus etoposide combination chemotherapy is associated with a relatively high frequency of FN, the risk factors are unclear. Hence, this retrospective study aimed to identify predictive markers of carboplatin/etoposide-induced FN. Methods: We conducted a retrospective cohort analysis of patients with previously untreated small-cell lung cancer (SCLC) who received combination chemotherapy with carboplatin (area under the concentration curve: 5 mg/mL·min, day 1) and etoposide (80 or 100 mg/m2, days 1–3) between July 2007 and June 2022. FN was assessed during the 21 days after initiation of carboplatin and etoposide therapy according to the Japanese Society of Medical Oncology’s definition. Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables were used to compare the two groups. Statistical significance was set at p values <0.05. Explanatory variables with p values <0.05 in the univariate analysis were included in the multivariate logistic regression analysis. Results: Among the 176 eligible patients, the incidence of FN during the first cycle of chemotherapy was 25.0% (44/176). Multivariate analysis revealed that co-administration of proton pump inhibitors (PPIs) or potassium-competitive acid blockers (PCABs) and body mass index (BMI) were significantly associated with FN (p = 0.0035 and 0.0011, respectively). Patients with both co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 presented with significantly higher frequencies of FN compared with the other patients (13/24 [54.2%] vs. 31/152 [20.4%] patients; odds ratio: 4.56, 95% confidence interval: 1.70–12.48; p = 0.00147). Conclusion: Patients who received carboplatin plus etoposide for SCLC with co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 more frequently present with FN than those without the two factors.

Efficacy of second-line chemotherapy after treatment with gemcitabine plus nab-paclitaxel or FOLFIRINOX in patients with metastatic pancreatic cancer

First-line chemotherapy for patients with metastatic pancreatic cancer (MPC) includes gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX). However, the efficacy of second-line chemotherapy and the role of combination chemotherapy in clinical practice is still unknown. Data was gathered from 14 hospitals in the Kyushu area of Japan from December 2013 to March 2017. The median overall survival (mOS) from second-line treatment was contrasted between patients who received second-line chemotherapy (CT group) and those who received the best supportive care (BSC group). Furthermore, the mOS of combination chemotherapy was compared to mono chemotherapy in the CT group. To control possible bias in the selection of treatment, we performed a propensity score-adjusted analysis. A total of 255 patients received GnP or FFX as first-line chemotherapy. There were 156 in the CT group and 77 in the BSC group of these. The CT group had a significantly longer mOS than the BSC group (5.2 vs. 2.6 months; adjusted hazard ratio (HR) 0.38; 95% CI 0.27–0.54). In the CT group, 89 patients received combination chemotherapy while 67 received mono chemotherapy. The mOS did not differ significantly between the combination and mono chemotherapy groups (5.5 vs. 4.8 months; adjusted HR 0.88; 95% CI 0.58–1.33). Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination chemotherapy conferred no improvement in survival compared to mono chemotherapy.

The impact of osteosarcopenia in patients with unresectable or recurrent biliary tract cancer receiving palliative chemotherapy.

Osteosarcopenia is a newly described syndrome that has been reported to be associated with worse outcomes in various types of cancer. However, its impact on survival in biliary tract cancer remains unclear. This study evaluated the impact of osteosarcopenia on survival in patients with unresectable or recurrent biliary tract cancer. A total of 306 patients with unresectable or recurrent biliary tract cancer who initiated chemotherapy at our institution between 2015 and 2021 were retrospectively investigated. Skeletal muscle index and bone mineral density were measured using pretreatment cross-sectional computed tomography images. Baseline characteristics and survival outcomes were compared between patients with osteosarcopenia and those without. The Cox proportional hazards regression model was used to identify factors associated with survival. Osteosarcopenia was present in 66 patients (22%) and was associated with older age (74 vs. 69years, P<0.001) and female sex (58 vs. 37%, P=0.003). Patients with osteosarcopenia tended to have worse performance status (P=0.098), higher modified Glasgow prognostic score (P=0.082), higher neutrophil to lymphocyte ratio (P=0.058) and were significantly less likely to receive combination chemotherapy (68 vs. 80%, P=0.044) than those without. Osteosarcopenia was associated with reduced survival (8.9 vs. 14.0months, P<0.001) and was identified as an independent factor predicting shorter survival in multivariate analysis. Osteosarcopenia was associated with poor survival in unresectable or recurrent biliary tract cancer treated with chemotherapy. This study highlights the potential importance of screening for osteosarcopenia in patients with biliary tract cancer.

Association between baseline radiological tumor burden and outcomes in patients with metastatic breast cancer treated with an immune checkpoint inhibitor.

1103 Background: Lower baseline radiological tumor burden is associated with more favorable outcomes for patients with metastatic non-small cell lung cancer and melanoma treated with immunotherapy. However, minimal data is available for metastatic breast cancer patients. This is despite immunotherapy, in combination with chemotherapy, now being standard-of-care for a subset of metastatic breast cancer patients who have triple-negative disease and are PD-L1 positive. Methods: We reviewed data of 82 patients with metastatic breast cancer consecutively treated at our institution from August 2015 to October 2021, who received &gt; 1 dose of an immune checkpoint inhibitor (anti-PD-1 or -PD-L1) within the context of a clinical trial. Baseline tumour burden was assessed by a single radiologist and calculated as sum of Response Evaluation Criteria in Solid Tumours 1.1 baseline target lesions (baseline tumour size [BTS]) or as sum of all measurable baseline lesions (total tumour burden [TTB]); the impact of both parameters on treatment outcomes was investigated. Treatment outcomes assessed were clinical benefit rate (complete response, partial response or stable disease for 6 months or more [CBR6]), disease free survival (DFS) and overall survival (OS). Multivariate analysis adjusted for ECOG status, line of treatment (first line vs second line or beyond), and whether immunotherapy was given in combination with chemotherapy or as monotherapy. Results: A total of 82 patients were included in the analysis. 43 patients (52%) received combination chemotherapy with immunotherapy, 39 patients (48%) received immune checkpoint inhibitor monotherapy. Median BTS and TTB were 36.5mm (range 0 -204mm) and 43mm (range 0 – 1123mm) respectively. CBR6 was significantly associated with BTS (p=0.004) and TTB (P=0.002) quartiles, with clinical benefit time progressively increasing with decreasing tumor burden quartiles. Both increasing BTS (p&lt;0.001) and TTB (p&lt;0.001) across quartiles were significantly associated with shorter OS. There was a numerical, but not statistically significant, association between both parameters as quartiles (BTS, p=0.25; TTB, p=0.07) and PFS. In the bottom BTS quartile, 32% of patients were progression-free and 95% alive at 12 months, compared with 15% and 40% respectively in the top quartile. Similar results were seen when TTB was used as the baseline measurement: 32% progression-free and 95% alive at 12 months in the bottom quartile compared with 1% and 33% in the top quartile. Multivariate analysis confirmed that both BTS and TTB, considered as continuous variables, are independently associated with OS. Conclusions: Lower baseline radiological tumor burden is associated with better outcomes in patients with metastatic breast cancer treated with immune checkpoint inhibitors.

Real-world retrospective review of monotherapy following platinum-based chemotherapy for metastatic urothelial cancer

To compare estimated survival times of patients who had received maintenance monotherapy with gemcitabine (GEM), or an immuno-oncology (IO) drug (i.e., pembrolizumab or avelumab) or both therapies (one after the other) following platinum-based combination chemotherapy for metastatic urothelial carcinoma (UC) in a real-world setting. For this retrospective study, we included consecutive patients with metastatic UC who had received first-line platinum-based chemotherapy followed by second-line treatment at our centre from March 2008 to June 2020. Of the 74 patients identified, 58 had received monotherapy as second line treatment, and 16 had received combination chemotherapy (i.e., non-monotherapy). The estimated median duration of survival was significantly longer in the monotherapy group compared with the non-monotherapy group (29 vs 7 months). Multivariate analysis showed that the outcome of the first-line chemotherapy treatment was the most important prognostic factor for survival. There was no significant difference in survival times between monotherapy with GEM or IO drugs. In addition, survival was significantly prolonged when GEM therapy was administered following IO drugs compared with GEM therapy alone. Monotherapy following primary chemotherapy for advanced UC significantly prolonged survival times, and IO drug therapy remained effective when followed by GEM single agent maintenance therapy.

Innovative approaches to the treatment of local recurrent vulvar cancer in patients with lichen sclerosus

Background. In recent years, there has been an increase in the incidence of vulvar precancer (lichen sclerosus), as well as vulvar cancer. Since this disorder is rare, treatment planning and therapy itself are often suboptimal, which results in a high recurrence rate. Treatment of patients with local recurrence is even more difficult. Improper therapy often leads to fatal outcomes.Aim. To develop an innovative therapeutic approach to local recurrent vulvar cancer that includes combination (intraarterial and systemic) chemotherapy and surgery.Materials and methods. This pilot study included two patients with a second episode of local recurrent vulvar cancer. The first patient was denied special treatment, whereas the second one was offered abdominoperineal resection of the rectum. At the first stage, the patients received combination chemotherapy; at the second stage, they had combination reconstructive surgeries.Results. Combination chemotherapy was highly effective as demonstrated by the reduction of the recurrent tumor to a resectable size. Combination and reconstructive surgeries allowed us to preform radical treatment and preserve functions of the adjacent organs.Conclusion. Combination treatment was highly effective in patients with local recurrent vulvar cancer, when the tumor was located near the urethra, vagina, and anus or invaded them. Combination chemotherapy ensured good tumor regression, while surgery gave hopes for a favorable outcome.

Treatment Outcome of Burkitt's Lymphoma in Adolescents and Adults: A Retrospective Study

Abstract Introduction Burkitt's lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma (NHL) having three distinct subtypes: endemic, sporadic, and immunodeficiency-associated BL. Sporadic BL accounts for only 1 to 2% of adult NHL. Objectives The objective of this article was to study the clinical profile and treatment outcome of patients with BL. Materials and Methods This was a retrospective study of 60 patients with BL conducted in the department of medical oncology at a tertiary cancer center in India during a 10-year period. Patients with BL/leukemia above 14 years of age diagnosed during the study period were included and their clinical presentation, treatment details, and outcome were studied. Results Among 60 cases with BL, there were 41 males and 19 females. The median age at presentation was 42 years (range: 14–81 years). The main symptoms were lymphadenopathy, abdominal pain, and abdominal distension. Two patients each had paraparesis, breast lump, and jaw swelling and one patient had involvement of the cervix. Thirteen patients had features of tumor lysis at presentation. The Ann Arbor stage was I in 17, II in 16, III in 5, and IV in 22. Fifty-five patients received combination chemotherapy that included hyper-cyclophosphamide, vincristine, adriamycin, dexamethasone ± rituximab (hyper-CVAD ± R; 35), cyclophosphamide, adriamycin, vincristine, prednisolone/ cyclophosphamide, vincristine, prednisolone ± rituximab CHOP ± R (13), Berlin-Frankfurt-Munich protocol (4), and others (3). Thirty-four patients attained remission, 13 patients had progressive disease, and 8 patients died during chemotherapy. At a median follow-up of 113 months, 58% patients were alive. Conclusions BL accounts for 1.57% of NHL above the age of 14 years with male preponderance. Intensive, short-duration chemotherapy is the standard treatment. Treatment with hyper-CVAD ± R gives 8-year progression-free survival and overall survival (OS) of 60%. Treatment with CHOP ± R is an alternative option in elderly frail patients with an 8-year OS of 46%.

Current Treatment Practices and Prognostic Factors in Early-Stage Ovarian Cancer—An Analysis of the NOGGO/JAGO

Surgery is the backbone of early-stage ovarian cancer (OC) management. However, in practice, there is disagreement about the extent of surgical staging and whether additional adjuvant treatment should be provided. As omitting relevant diagnostic or therapeutic procedures might lead to undertreatment, we aimed to structurally investigate treatment practice in addition to prognostic factors in a multicentre series of patients (pts) diagnosed with early-stage OC. Within this retrospective, multicentre study, medical records of 379 pts who had undergone surgery for suspected early-stage OC between January 2014 and March 2020 were analysed. Of the 379 patients, 292 had pT stage 1a-2a and had complete data on the extent of surgical staging. At least one surgical step was omitted in 100 pts (34.2%). Complete surgical staging (n = 192; (65.8%)) was more often performed in high-grade serous OC and was independent of the healthcare level of the hospital where the initial diagnosis was made. Missing to take peritoneal biopsies was associated with reduced relapse-free-survival in incompletely staged, pT1 cases (p = 0.03). About every second patient (46.7%) with a final stage lower than FIGO IIB and treated with adjuvant chemotherapy received combination chemotherapy. BRCA1 and BRCA2 testing was only performed in a subset of pts, and mutations were detected in 18% (14/79) and 9% (7/85) pts, respectively. This study helps to increase our understanding of early-stage OC treatment and prognosis. In addition to treating patients in compliance with current guidelines, the need for BRCA testing should also be considered for early-stage OC.

End-of-Life Care of Acute Myeloid Leukemia Compared with Aggressive lymphoma in Patients Who Are Eligible for Intensive Chemotherapy: An Observational Study in a Japanese Community Hospital.

Patients with hematological malignancies (HMs) are reported to receive more aggressive care at the end of life (EOL) than patients with solid tumors. However, the reasons behind this occurrence are not fully understood. To examine whether the care at EOL for HMs is mainly because of the disease characteristics or hematologists' attitudes and systems of care, we compared the EOL care of patients with acute myeloid leukemia (AML) and diffuse large B cell lymphoma (DLBCL). We retrospectively analyzed the EOL care of patients with AML and DLBCL younger than 80 years who were receiving combination chemotherapy at a city hospital in Japan. Fifty-nine patients with AML and 65 with DLBCL were included. Those with AML received chemotherapy more often within their last 30 days (48% vs. 19%, p < 0.001) and 14 days (37% vs. 1.5%, p < 0.001) of life, and consulted the palliative team less frequently (5.3% vs. 29%, p < 0.001). In the last 3 years, the mortality rate in hematological wards decreased from 74% to 29% in the DLBCL group, but only from 95% to 90% in the AML group. In multivariate analysis, AML (odds ratio [OR] 0.065) and death before 2018 (OR, 0.077) were significant factors associated with reduced referrals to specialized palliative teams. Patients with AML tend to have lesser access to specialized palliative care and fewer options for their place of death than those with DLBCL. Detailed EOL care plans are needed for these patients, considering the characteristics of the disease.

Abstract P2-23-01: Patient-derived xenografts allow deconvolution of single agent and combination chemotherapy responses in triple-negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC) patients frequently receive combination chemotherapy treatment, but a direct comparison of response to carboplatin, docetaxel, and their combination in 50 TNBC patient-derived xenografts (PDXs) showed that combination treatment was largely ineffective at generating enhanced responses over the best single agent. This suggests de-escalation of chemotherapy may be possible if molecular mechanisms and biomarkers underlying response to individual treatments can be identified. To this end, we performed multi-omics profiling for the 50 TNBC PDXs. Methods: Orthotopic TNBC PDXs were treated with four weekly cycles of docetaxel, carboplatin, or the combination. Changes in tumor volume after 4 weeks of treatment were assessed quantitatively and by modified RECIST criteria. Genomic, transcriptomic, and mass-spectrometry-based proteomic profiling were performed on baseline tumors prior to treatments to identify associations with chemotherapy response at the gene and pathway level. ProMS was used to integrate both RNA and protein data to select a 5 RNA feature combination for optimized prediction of carboplatin response in a logistic regression model. Publicly available neoadjuvant chemotherapy clinical datasets with transcriptomic data and response information used for validation/testing included TNBC samples from: GSE18864, I-SPY2 (GSE194040), and BrighTNess (GSE164458). Results: Proteogenomic profiles revealed distinct genes associated with response to each agent and their combination, respectively, suggesting distinct molecular mechanisms underlying response to each treatment. A substantial number of genes associated with single agent and combination treatment were validated in multiple independent patient cohorts receiving platinum and taxane containing neoadjuvant therapy, confirming clinical relevance of our PDX panel. For the same treatment, different types of molecular data identified distinct sets of associated genes, providing highly complementary information. At the pathway level, RNA and protein data converged to metabolic and E2F/G2M related pathways which were upregulated in PDXs resistant or responsive to all treatment types, respectively, while variable levels of MYC-related proliferation pathways were observed across all treatments suggesting pathways that are common across and unique to different treatments. Several individual genes found to be higher in PDXs with better response to either single-agent had discriminatory power in external clinical TNBC datasets treated with similar neoadjuvant chemotherapy regimens. In addition, a logistic regression-based carboplatin response prediction model trained to select a group of 5 RNA markers (TKT, MAGI2, ATF6B, MCM7, LRP6) using both RNA and protein data performed the best in predicting response to cisplatin in a clinical TNBC dataset vs predicting response to other datasets with taxane and platinum + taxane combination containing chemotherapy regimens, demonstrating specificity of the prediction model. These results suggest potential individual biomarkers or biomarker combinations to select TNBC tumors that may respond to either single agent carboplatin, docetaxel, or their combination. PDXs refractory to all treatment arms had higher levels of proteostasis-related pathways including proteasome degradation and the unfolded protein response (UPR) related to endoplasmic reticulum stress and altered levels of chromatin regulation. Subsequent pharmacological targeting of the UPR pathway and targeting HDACs enhanced chemotherapy response. Conclusion: Proteogenomic characterization identifies molecular mechanisms and putative biomarkers for stratifying TNBC tumors for single or combination chemotherapy treatments, suggests targeted therapies to augment chemotherapy response, and provides a valuable resource for researchers and clinicians. Citation Format: Jonathan T. Lei, Chen Huang, Ramakrishnan R. Srinivasan, Suhas Vasaikar, Lacey E. Dobrolecki, Alaina N. Lewis, Na Zhao, Jin Cao, Susan G. Hilsenbeck, C. Kent Osborne, Mothaffar Rimawi, Matthew J. Ellis, Varduhi Petrosyan, Alexander B. Saltzman, Anna Malovannaya, John D. Landua, Bo Wen, Antrix Jain, Gerburg M. Wulf, Shunqiang Li, Daniel C. Kraushaar, Tao Wang, Xi Chen, Gloria V. Echeverria, Meenakshi Anurag, Bing Zhang, Michael T. Lewis. Patient-derived xenografts allow deconvolution of single agent and combination chemotherapy responses in triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-01.

Clinical features of gestational choriocarcinoma: A retrospective bicentric study.

To investigate the clinicopathological features, prognostic factors, treatment, clinical response, and outcome of gestational choriocarcinoma (GCC). A retrospective review was made of the clinicopathological and survival data of 13 patients who were diagnosed and treated for GCC in two referral centers in Turkey between 1992 and 2020. The median age of patients was 36 years (range, 27-54 years), and seven were ≤39 years. The antecedent pregnancy was a term in nine (69.2%) cases, and the risk score was ≥7 in 11 (84.6%). According to the International Federation of Gynecology and Obstetrics 2009 staging, eight cases were in stage I, two in stage III, and three in stage IV. With the exception of one patient, all the others received combination chemotherapy (CT), and two of those were also treated with radiotherapy. Chemoresistance developed in 50% (6/12), and second-line CT was given to four of these. The overall complete response rate was 69.2%. Four patients died of chemoresistance and disease progression, all of them were with antecedent-term pregnancy, had high scores ≥7, and had metastases. GCC is a unique subtype of gestational trophoblastic neoplasia, which differs from others in terms of poor prognosis, a frequent tendency to early metastasis, and resistance to treatment. To be able to achieve the most efficient therapy and prognosis, histopathology-based risk models should be developed.

Clinicopathological features of HER2-low expressed advanced gastric cancers.

459 Background: The DESTINY-Breast04 data demonstrated the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) was also effective for metastatic breast patients (pts) with HER2-low expression. Now that the HER2-low expressed cancer is categorized as an independent subset in breast cancer patients. It is unknown whether patients with the HER2-low expression are distinguishable from the HER2 negative or positive and are potential candidates for the anti-HER2 therapy in advanced gastric cancer (AGC) patients. Methods: We retrospectively reviewed the medical records of AGC pts who received standard chemotherapy with platinum containing regimens as the first-line treatment between Jan, 2011 and Dec, 2018 at the Cancer Institute Hospital of the JFCR. AGC pts were classified according to the HER2 status using immunohistochemistry (IHC) and in situ hybridization (ISH) as follows; HER2 negative (IHC 0), HER2-low (IHC 1+ or 2+/ISH-) and HER2 positive (IHC2+/ISH+ or 3+). This study was conducted to investigate the clinicopathological features and prognosis of HER2-low AGC pts compared with HER2 negative and positive. Results: A total of 734 AGC pts were received HER2 testing and classified into three groups according to HER2 status (HER2 negative; n=410, HER2-low; n=154, HER2 positive; n=170). The proportion of male (negative; 61.5%, low; 63.6% and positive; 69.4%), intestinal histology (negative; 21.0%, low; 44.2% and positive; 59.8%), liver metastases (negative; 18.3%, low; 24.8% and positive; 46.5%), higher serum CEA level (&gt;ULN) (negative; 32.2%, low; 41.6% and positive; 56.5%) and higher serum CA19-9 level (&gt;ULN) (negative; 34.1%, low; 36.7% and positive; 56.5%) were gradually increased along with HER2 expression level. The proportion of peritoneum metastasis (negative; 56.3%, low; 44.8% and positive; 21.8%) was decreased along with the HER2 expression level. One hundred and fifty-two pts (89.4%) received combination chemotherapy with trastuzumab in the first-line treatment. Sixteen pts received trastuzumab in the HER2-low (n=3) and HER2 negative (n=13) in the clinical trial. The median survival time (MST) of pts with HER-low was the same with that of HER2 negative (15.7ms). The statistically significant difference was observed in OS between the HER2-low and HER2 positive (HR 1.43 95% CI: 1.12-1.83, P=0.003). Conclusions: AGC Pts with HER2-low have intermediate clinicopathological features between HER2 negative and positive. A Novel effective anti-HER2 therapy for the HER2-low expressed tumor would be warranted in AGC treatment.