Median Disease-free Interval Research Articles

Posterior retroperitoneal adrenalectomy for metastatic disease: a multi-site Australian series.

Posterior retroperitoneoscopic adrenalectomy (PRA) for isolated adrenal metastasis is minimally invasive, may prolong survival and improve quality of life. The current evidence base is scant. A multi-site retrospective analysis of all cases of PRA for adrenal metastasis between 2011 and 2023, by four high-volume adrenal surgeons was performed. Perioperative morbidity, disease-free and survival outcomes were reported. Of 51 patients, 34(67%) male, mean age 63 ± 12 years, mean BMI 28; 49 PRAs for adrenal metastatectomy were completed (one abandoned due to tumour unresectability, one conversion to anterior laparoscopic approach) across 11 hospitals (49% public). Primary tumours included: 11 colorectal, 11 renal, 8 lung, 6 hepatocellular, 4 sarcoma, 3 breast, 2 melanoma, 2 ovarian and 1 each of pancreatic, oesophageal, testicular and prostate cancer. There were 12 synchronous (<6 months) and 39 metachronous (>6 months after primary diagnosis) tumours; 21 (42%) left sided, none bilateral. Mean operative time was 95 ± 34 minutes, mean maximal tumour diameter was 34 mm ± 13 mm and median length of hospitalization 1 ± 1 days. There were 8 (16%) complications; 1 ICU admission, 1 re-admission for pneumonia and 6 Clavien-Dindo grade I complications. There were 10 (20%) mortalities and a median overall survival of 29 months (range 7-123, n = 41). Disease recurred in 15 (40%) patients (n = 37), with a median disease-free interval of 18 months (range 1-68). Port site recurrence occurred in 2 patients, both simultaneously with disseminated metastases. In carefully selected patients with adrenal metastases, PRA by high-volume adrenal surgeons has minimal morbidity and short hospitalization. Surgery should be considered prior to local ablation.

Abstract B022: Immediate post-treatment detection of minimal residual disease in HPV-Driven oropharyngeal cancer is associated with high risk of recurrence

Abstract Purpose: Detecting minimal residual disease (MRD) has emerged as a key strategy in oncology for identifying those at high risk of relapse. Circulating tumor tissue modified viral (TTMV)-HPV DNA has emerged as a promising biomarker in HPV-driven oropharyngeal cancer. Prior studies have largely focused on detection beyond three months post-treatment. This study evaluated the ability of TTMV-HPV DNA to detect MRD immediately after initial or salvage treatment. Patients and Methods: This IRB-approved, retrospective cohort study included 171 patients across eight U.S. centers who had pathologically confirmed HPV-driven oropharyngeal cancer. Patients received at least one TTMV-HPV DNA test (NavDx®, Naveris, Inc.) done between zero and three months of treatment between February 2020 and April 2022. Minimum four months of follow-up was required for patient inclusion. Test results were correlated with physician-reported exams, imaging studies, and biopsies. Results: Patients were primarily White (94%) and male (86%) and were a median age at diagnosis of 60 years (range: 31 - 81). Primary tumors were located in the tonsil or base of tongue (94%) and were mostly T1-T2 (77%), N1 (66%), and M0 (98%). Patients had a median follow-up of 17 months after the completion of initial definitive treatment (range: 4-96 months). In this cohort, 198 tests conducted in 171 patients were evaluable. A total of 14 patients had both biopsy-confirmed pathologic recurrences and relevant post-treatment testing data in relation to the recurrence, with a median disease-free interval of three months (range: 1-16). Within this cohort, TTMV-HPV DNA testing demonstrated a per-patient sensitivity of 85.7% (12/14, 95% CI: 67-100). The positive predictive value (PPV) of a single TTMV-HPV DNA test within the first three months following treatment was 86.7% (13/15, 95% CI: 69.5-100). Six of the positive tests (46.2%) preceded clinical recurrence detection by a median lead-time of 36 days (range: 21-97). Test positivity following initial definitive treatment was significantly associated with worse recurrence-free survival (log-rank test, p&amp;lt;0.0001; hazard ratio: 21). The two patients with false positive test results had their TTMV-HPV DNA testing performed just four days after completing CRT. Their test scores returned to negative on the subsequent test, and both patients have remained disease-free. Of the 157 patients who remained TTMV-HPV DNA negative throughout the duration of follow-up, only two (1.3%) had biopsy-confirmed, HPV-positive recurrence before or within three months of a negative test. The specificity and negative predictive value (NPV) per-test were each 98.9% (181/183, 95% CI: 97.4-100). Conclusion: TTMV-HPV DNA demonstrates strong potential as a prognostic biomarker for detecting MRD in the immediate post-treatment setting, with a high PPV and NPV for recurrence. These findings support the integration of TTMV-HPV DNA into routine surveillance protocols to enhance early detection of recurrence and guide timely interventions. Citation Format: Scott A Roof, James Jabalee, Eleni M Rettig, Rocco Ferrandino, Sida Chen, Marshall R Posner, Krzysztof J Misiukiewicz, Eric M Gender, Raymond L Chai, John Sims, Elaine Thrash, Scott J Stern, Noah S Kalman, Sreenija Yarlagadda, Adam Raben, Lydia Clements, Abie Mendelsohn, John M Kaczmar, Yadav Pandey, Mihir Bhayani, Catherine DV Fitz, Glenn J Hanna. Immediate post-treatment detection of minimal residual disease in HPV-Driven oropharyngeal cancer is associated with high risk of recurrence [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B022.

Intraoperative Radiation Therapy for Recurrent Cervical and Endometrial Cancer: Predicting Morbidity and Mortality in a Contemporary Cohort.

Our objective was to describe the use of intraoperative radiation therapy (IORT) for the treatment of recurrent/persistent cervical or endometrial cancer and assess predictors of postoperative complications and 3-year mortality. In this multi-site retrospective study, data were abstracted for recurrent/persistent endometrial or cervical cancer patients who underwent IORT from June 2004 to May 2021. Complications were graded on the six-point Accordion scale. Variables associated with complications were analyzed with univariate logistic regression, while variables associated with death within 3 years were analyzed with Cox proportional hazards modeling. Survival was analyzed with the Kaplan-Meier method. Eighty patients had planned IORT for recurrent/persistent endometrial (n = 35) or cervical cancer (n = 45). The mean age of the cohort was 56.8 years (SD = 13.7), and the median disease-free interval from primary disease to recurrence was 20.0 months (IQR 10.0-63.1). The overall survival at 3 years was 48.6% (95% CI: 38.3-61.6%) with a median survival of 2.8 years. Within 30 days postoperative, 16 patients (20.1%) had grade 3-5 complications and one death (1.3%) occurred. Factors associated with grade 3+ complication included ECOG PS 2-3 (OR 18.00, p = 0.04), neoadjuvant chemotherapy and/or immunotherapy (OR 6.98, p < 0.01), and pelvic sidewall involvement (OR 8.80, p = 0.04). Factors associated with death within 3 years of surgery included ECOG PS 2-3 (HR 8.97, p < 0.01), neoadjuvant chemotherapy and/or immunotherapy (HR 2.34, p = 0.03), whether exenteration was performed (HR 2.64, p = 0.01), and positive resection margin (HR 3.37, p < 0.01). In well-selected patients, IORT is a feasible and safe option for the treatment of recurrent/persistent gynecologic malignancy with an appreciable survival benefit.

Real-World Clinical Outcomes of Treatment With Olaparib for BRCA1/2 Mutation-Positive Metastatic Breast Cancer in Japanese Patients.

Background Olaparib is effective in the treatment of metastatic breast cancer (MBC) patients, mainly confirmed by deleterious germline BRCA mutations. However, real-world data are scarce. Methodology A total of 10 cases from our institute and 17 cases from the relevant Japanese literature were reviewed. All 27 patients had MBC with confirmed deleterious germline BRCA mutations. Tumor reduction, response duration, disease-free interval (DFI), overall survival (OS), and safety were assessed. Additionally, exploratory research was conducted on the characteristics of a subgroup of patients who had a long-term response to olaparib. Results In the 10 cases from two Juntendo hospitals who received olaparib from July 2018 to December 2021, the median age was 48 years (range = 37-63 years). The same numbers of BRCA1 and BRCA2 mutations and the same ratios of luminal and triple negative (TN) breast cancer cases were observed. The metastatic sites, mainly visceral, included the lungs (n = 4), liver (n = 5), and bone (n = 6). The median duration of drug use was four months (range = 1-36 months). The median number of treatment regimens from metastasis to olaparib administration was 2.0 (range = 1-9 regimens). The median DFI was 21 months (range = 0-106 months). The median OS was not reached (range = 16-191 months). In the subgroup analysis of six cases in which olaparib was effective for four months or more, there was a case where DFI was longer than 100 months. Treatment-related toxicities (TRTs) included neutropenia (n = 5; 50%), anemia (n = 4; 40%), thrombocytopenia (n = 2; 20%), nausea (n = 1; 10%), and fatigue (n = 1; 10%). CTCAE (version 5.0) grade ≥3 TRTs included anemia (n = 1; 10%) and neutropenia (n = 5; 50%). On the other hand, neutropenia was previously said to be as low as 27.3%, lower than anemia (40.0%), in a population including various races. We additionally examined another 17 cases from the Japanese literature. Conclusions To our knowledge, this study reports the first real-world data of Japanese patients with MBC and confirmed deleterious germline BRCA mutations. Our data showed that olaparib is effective in the real world. The incidence of neutropenia seemed higher in Japanese patients.

The SRC-family serves as a therapeutic target in triple negative breast cancer with acquired resistance to chemotherapy.

Resistance to chemotherapy, combined with heterogeneity among resistant tumors, represents a significant challenge in the clinical management of triple negative breast cancer (TNBC). By dissecting molecular pathways associated with treatment resistance, we sought to define patient sub-groups and actionable targets for next-line treatment. Bulk RNA sequencing and reverse phase protein array profiling were performed on isogenic patient-derived xenografts (PDX) representing paclitaxel-sensitive and -resistant tumors. Pathways identified as upregulated in the resistant model were further explored as targets in PDX explants. Their clinical relevance was assessed in two distinct patient cohorts (NeoAva and MET500). Increased activity in signaling pathways involving SRC-family kinases (SFKs)- and MAPK/ERK was found in treatment resistant PDX, with targeted inhibitors being significantly more potent in resistant tumors. Up-regulation of SFKs- and MAPK/ERK-pathways was also detected in a sub-group of chemoresistant patients after neoadjuvant treatment. Furthermore, High SFK expression (of either SRC, FYN and/or YES1) was detected in metastatic lesions of TNBC patients with fast progressing disease (median disease-free interval 27 vs 105 months). Upregulation of SFK-signaling is found in a subset of chemoresistant tumors and is persistent in metastatic lesions. Based on pre-clinical results, these patients may respond favorably to treatment targeting SFKs.

FP1.8 - Optimizing Rectal Cancer Treatment: Comprehensive response to Neoadjuvant therapy

Abstract Aims This study aimed to assess the outcomes and feasibility of a watch-and-wait strategy in patients with rectal cancer showing a complete response to neoadjuvant chemoradiotherapy (CRT). The primary objectives included evaluating the oncological results, disease-free interval, and survival rates in patients who underwent the watch-and-wait approach after a complete clinical response. Methods The study involved a retrospective analysis of last 10 years of rectal cancer patients enrolled in a complete responder surveillance program in an acute general hospital. Cohort characteristics, including age, performance status, tumor histology, distance from the anal verge, and treatment modalities, were documented. Results The median age was 74 (57-90), and the median performance status was 1, with the age at diagnosis being 69. All cohort members had a histologically confirmed rectal adenocarcinoma. The median tumor-to-anal-verge distance was 5 cm (1-10 cm). Neoadjuvant chemotherapy was administered to 55% of patients. All patients underwent long-course radiotherapy, and 35% received papillon contact brachytherapy. Total neoadjuvant therapy was received by 10%. The median follow-up involved approximately 9 colonoscopies. During follow-up, 25% of patients experienced recurrence, with a median disease-free interval of 3.5 years. Conclusion The findings of this study, in addition to ongoing prospective clinical trials and insights from databases such as EURECCA and OnCore, indicate that a watch-and-wait approach can be safe and effective for selected rectal cancer patients who have achieved a complete response to neoadjuvant CRT. This study highlights the significance of additional research to identify appropriate patients for this approach and to refine its implementation in rectal cancer management.

Salvage Radiotherapy for Loco-Regional Recurrence of Esophageal Cancer Following Surgery.

There is few evidence regarding the optimal salvage treatment options for loco-reginal recurrence of esophageal cancer. This study aimed to evaluate the clinical outcomes of salvage radiotherapy (RT) in patients with loco-regional recurrence (LRR) after surgery for esophageal cancer. We retrospectively reviewed 147 esophageal cancer patients who received salvage RT for loco-regional recurrence between 1996 and December 2019. A total dose of 60 Gy in 20 fractions was used for RT alone and 60-70 Gy in 30-35 fractions for concurrent chemoradiotherapy (CCRT). The patients' median age was 65 (41-86). The median disease-free interval (DFI) was 13.5 months (1.0 to 97.4 months). After a median 18.8 months follow-up, the 2-year overall survival (OS) and progression-free survival (PFS) rates were 38.1% and 25.9%, respectively. The median OS and PFS were 18.8 and 8.4 months, respectively. The CCRT could not improve OS compared to RT (p=0.336), but there was a trend of better PFS in the CCRT group. Regarding toxicities, the rate of grade 3 or higher toxicity was 10.9% occurring in 16 patients, and it was higher in patients who received CCRT than in the RT alone group (19.6% vs. 6.3%, p=0.023). Salvage RT alone as well as CCRT could be effective in patients with locoregionally recurrent esophageal cancer.

Description of outcome and adverse events in 21 cats with locally advanced nasal planum squamous cell carcinoma treated with electrochemotherapy.

Squamous cell carcinoma (SCC) is the most common tumour in the nasal planum of cats. Surgery has traditionally been the treatment of choice but might not be feasible in locally advanced scenarios. Electrochemotherapy (ECT) has shown good control in superficial tumours, but there is a lack of robust information about efficacy in locally advanced cases. The aim of this study was to assess the safety and efficacy of ECT in the treatment of locally advanced stage nasal planum SCC in cats. The clinical database of a veterinary referral hospital was searched retrospectively for cats diagnosed with a locally advanced nasal planum SCC (T3N0M0 or T4N0M0) that had received ECT. Local response, adverse events and outcome were documented. The data were evaluated by inferential statistics and correlations between response, recurrence, feline immunodeficiency virus/feline leukaemia virus status, number of treatments, voltage and severity of adverse events, with Kaplan-Meier curves and log-rank tests. Statistical significance was set at P <0.05. In total, 21 cats were enrolled over a 4-year period. Nineteen cats achieved a complete response (CR) and two cats a partial response (PR) for an overall response rate of 100%. Cats achieving a CR had a median disease-free interval of 182 days (range 128-327) and those with a PR had a median progression-free survival of 156.5 days (range 122-191). The median time to progression was not reached. The overall survival was 453 days for a median follow-up of 341 days (range 191-989). Of the cats, 62% had grade 3 or 4 toxicities, but no deaths due to the treatment were documented. Only voltage was correlated with longer survival (P = 0.001). ECT appears to be an effective treatment for feline nasal planum SCC and could be considered a first-line therapy for locally advanced cases. Toxicities reported can be severe in the short term and these could be secondary to more invasive lesions and equipment used.

Use of Lomustine and Prednisolone as First-Line Treatment in Canine Multicentric Lymphoma.

Multiagent chemotherapy is considered the most effective treatment for canine high-grade lymphoma; however, due to cost and time requirements, single-agent protocols have also been described. The aim of our study was to evaluate the outcome and prognostic factors of dogs affected by multicentric lymphoma treated with lomustine and prednisolone as first-line treatment. Cases of medium-large-cell multicentric lymphoma treated with lomustine and prednisolone were included in the study. Response to therapy, time to progression (TTP), median disease-free interval (MDFI) and median survival time (MST) were retrospectively described. Thirty cases were included. Eleven (36.67%) were T cell, 11 (36.67%) were B cell and 8 (26.66%) had unknown immunophenotype. The overall response rate (RR) was 87%, with 15 patients achieving CR (50%) and 11 patients PR (37%). The median TTP, MDFI and MST were 42, 63 and 90 days, respectively. The only factor significantly associated with MDFI and MST was the stage. Dogs with multicentric lymphoma treated with lomustine and prednisolone have lower RR, TTP, MDFI and MST compared with dogs receiving multiagent protocols. Based on the short-lasting response, this study confirms that this protocol might have minimal utility beyond palliation.

Correlation of previous local vaccination site “flares” during immunotherapy for metastatic melanoma with complete responses to therapy.

e21534 Background: mRNA vaccines have been shown to stimulate T-cells targeting patient-specific tumor neoantigens. When combined with immune checkpoint inhibitors (ICI) in a randomized Phase II trial, mRNA vaccines demonstrated improvement in recurrence free survival and distant metastasis free survival compared to ICI alone. We retrospectively examined patients (pts) with advanced melanoma treated more than 5 years ago on clinical trials with adjuvant NYESO1 or mRNA vaccine therapies (VT) then ICI upon recurrence and analyzed biomarkers correlating with treatment response. Methods: This retrospective study examined 22 pts with advanced melanoma treated between 2004-2017 with adjuvant vaccine therapies (VT). 10 of the 22 pts subsequently developed recurrent disease and were treated with ICI. We evaluated disease free interval following ICI, sex, age, BRAF status, HLA type, site of primary and metastatic disease, initial vaccine treatment, vaccine toxicities, stage and sites of melanoma recurrence, ICI treatment, response and toxicities, vaccine site flares or cutaneous immune related adverse events (irAEs) following ICI. Results: Of the 22 patients (11 male, 11 female) treated with adjuvant VT, median age at first vaccine was 53 years old. HLA type was known for 11 pts. Stage at initial VT was IIB to IIIC. 14 pts recurred following adjuvant VT. Median time from vaccine initiation to melanoma recurrence was 3.2 years (range 6.5 months to 11 years). 10 pts received ICI for recurrent melanoma, 3 pts received ipilimumab, 2 anti-PD1 monotherapy, 4 ipilimumab and nivolumab, and 1 nivolumab/relatlimab. Stage at first ICI was IIIB to IV M1d. 9 pts experienced cutaneous irAEs. 7 pts experienced local vaccine site flare reactions following ICI treatment. Additionally, 2 pts experienced vitiligo, 2 with dermatologic flares (bullous pemphigoid and psoriatic rash), 2 with generalized rash that resolved with steroid cream. 1 pt did not experience rash, vaccine site flare, nor irAE dermatologic flare. Of the pts who recurred, 2 pts had BRAF V600E mutations, and 1 of these pts experienced vaccine flare, the other did not. 1 pt with a BRAF Q16L mutation did not have vaccine flare. 6 out of 7 BRAF wild type pts who recurred and received ICI experienced a localized vaccine site flare. Median disease-free interval following ICI treatment was 1.5 years (range 3 months to 9 years). All 10 pts are disease-free and off ICI being closely monitored. Conclusions: Evidence of prior localized vaccination “flare” may be a biomarker for a complete immunologic response in pts with metastatic disease treated with immunotherapy. ICI targeting CTLA-4 and/or PD-1 both triggered this localized vaccination site response, suggesting that T cell memory and immunologic activation against melanoma antigens translate into clinical responses.

Abstract PO5-05-14: Survival in Young Women with De Novo or Recurrent Metastatic Breast Cancer

Abstract Background. Approximately 12,000 women aged 40 years or younger are diagnosed with breast cancer every year in the United States alone. Limited data exist regarding survival in young women with metastatic breast cancer (MBC), particularly when considering modern tumor subtyping and treatment, though previous studies have suggested that patients presenting with MBC at diagnosis (de novo stage IV) have better prognosis than those who develop recurrent MBC after initial diagnosis of stage 0-III disease. We sought to determine survival rates in young patients with MBC stratified by disease presentation (de novo versus recurrent) and subtype. Methods. The Young Women’s Breast Cancer Study (YWS) is a multicenter, prospective cohort which enrolled 1,302 women diagnosed with stage 0-IV breast cancer at age ≤40 from 13 North American academic and community-based sites from 2006-2016. The current median follow-up is 10.1 (range 0.4-16.3) years. Histopathology slides were centrally reviewed for 97% of the participants, and clinical tumor molecular subtypes have been detailed. In the recurrent group, receptors were obtained from the initial breast surgery. Descriptive analyses were used to characterize patients with de novo or recurrent MBC, including demographic and disease characteristics, and survival rates. Overall survival was estimated using the Kaplan-Meier method and compared by log-rank test between those who presented with de novo and relapsed disease overall and within tumor subtypes. Results. Among 246 patients included in this analysis, 74.0% (n=182) had recurrent MBC and 26.0% (n=64) had de novo MBC. Most patients were white (n=208, 84.6%), while 6.9% were Asian (n=17), 4.5% Black (n=11), 0.8% Native American (n=2), 0.8% multiracial (n=2) and 2.4% other/unknown (n=6). A total of 4.5% of patients were Hispanic (n=11). Median age at diagnosis of de novo MBC was 37 years and 40 years for diagnosis of metastasis in the recurrent group. Median disease-free interval was 3.23 (range 0.32 – 13.84) years for the recurrent MBC group. Among all patients with MBC, most (55.7%, n=137) had estrogen receptor (ER) and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, whereas 17.9% (n=44) had ER and/or PR-positive HER2-positive, 7.3% (n=18) had ER/PR-negative HER2-positive, and 18.7% (n=46) had triple-negative tumors. A greater proportion of participants (43.8%, n=28) had HER2-positive disease in the de novo group than in the recurrent group (18.7%, n=34), P=&amp;lt; 0.0001. A total of 10.9% (n=7) of de novo patients had a germline BRCA mutation, compared to 13.7% (n=25) in the recurrent group. Median survival was 5.09 (95% CI: 3.74 – 6.38) years in the de novo group and 2.63 (95% CI: 1.98 – 3.21) years in the recurrent MBC group (P=0.0004). When stratifying by subtype, survival among patients with de novo ER and/or PR-positive HER2-positive disease was longer than among patients with recurrent disease (P=0.0149), whereas there were no statistically significant differences in survival between the de novo and recurrent disease groups in other disease subtypes (Table 1). Conclusion. Survival in young women with MBC is highly heterogeneous and varies substantially by tumor subtype and disease presentation. Those with de novo ER and/or PR-positive HER2-positive subtype appear to have better outcomes than those with recurrent MBC with the same subtype. These findings can inform patient care and potential future research to improve outcomes for young patients with MBC. Table 1: Median survival by disease presentation and subtype * 1 patient with recurrent MBC was not included because the initial diagnosis was DCIS MBC: metastatic breast cancer; OS: overall survival; CI: confidence interval; ER: estrogen receptor; PR: progesterone receptor; HER2: human epidermal growth factor receptor 2 Citation Format: Leticia Varella, Yue Zheng, Shoshana Rosenberg, Gregory Kirkner, Craig Snow, Kathryn Ruddy, Rulla Tamimi, Jeffrey Peppercorn, Lidia Schapira, Virginia Borges, Steven Come, Laura Collins, Ellen Warner, Kate Dibble, Eric Winer, Ann Partridge. Survival in Young Women with De Novo or Recurrent Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-14.

Abstract PS04-02: BRCA testing and PARP inhibitor utilization in real-world HER2-negative metastatic breast cancer

Abstract Background: PARP inhibitors (PARPi) have demonstrated progression-free survival benefits vs. chemotherapy in patients (pts) with metastatic breast cancer (mBC) and germline BRCA mutations (gBRCAm). NCCN guidelines recommend that all pts with mBC are offered gBRCAm testing to aid in systemic treatment decisions with PARPi. Understanding real-world gBRCAm testing patterns and PARPi use would be beneficial for improving clinical outcomes of pts with gBRCAm mBC. Methods: This retrospective cohort study identified pts ≥ 18 years old with HER2-negative mBC, diagnosed from 2014 to 2022 (US Flatiron Electronic Health Record database). gBRCAm testing patterns in mBC over time were examined by BC subtype (hormone receptor-positive [HR+] or triple-negative breast cancer [TNBC]) and disease stage at diagnosis [de novo or recurrent]). Timing of gBRCAm testing and subsequent initiation of first-line or later PARPi in pts with gBRCAm HR+ and TNBC mBC was assessed in pts diagnosed after 2018 when PARPi were approved in mBC. Prevalence of gBRCAm was calculated overall and by mBC subtype. Demographic and clinical characteristics were described by gBRCAm testing and PARPi initiation (yes/no). Real-world overall survival (OS) by PARPi use since mBC diagnosis was estimated using the Kaplan-Meier method and a log-rank test. Results: Of 15,006 total pts, 4654 (31.0%) had a gBRCAm test. Compared with pts who were not tested, gBRCAm-tested pts were younger at initial mBC diagnosis (median age: 53.5 vs. 62.0 years), had a shorter median disease-free interval before mBC diagnosis (821 vs. 959 days), and were less likely to have de novo mBC (28.0% vs. 31.2%). gBRCAm testing prevalence was 6.1% in the HR+ group (n=11,945) and 8.9% in the TNBC group (n=2430). gBRCAm testing rates mostly increased from 2014 to 2022 and were lowest in HR+ tumor subtypes; &amp;lt; 2/3 of all pts had a gBRCAm test from 2020 onwards (Table). Most pts with recurrent mBC (HR+: 68.3%; TNBC: 76.1%) were gBRCAm tested before diagnosis, whereas pts with de novo mBC were tested at a later timepoint ( &amp;gt; 60 days after mBC diagnosis – HR+: 48.3%; TNBC: 38.4%). Of all pts with gBRCAm diagnosed from 2018 onwards (n=187), 44.4% initiated PARPi. A higher proportion of pts with gBRCAm in the TNBC group initiated PARPi (52.9%) than in the HR+ group (42.4%). Pts with gBRCAm in the TNBC group received PARPi earlier than pts with gBRCAm in the HR+ group (mean days from mBC diagnosis to first PARPi use: 173 and 411 days, respectively). Fewer pts with de novo mBC (35.7%) initiated PARPi than pts with recurrent mBC (50.8%). With a median follow-up of 15.3 months, pts with gBRCAm initiated on PARPi had numerically longer median OS (32.3 months [95% CI: 24.2–47.4]) than PARPi non-initiators (21.4 months [95% CI:18.4–43.5]). OS results should be regarded with caution due to the small sample size (n=187). Conclusions: Despite NCCN guideline gBRCAm-testing recommendations, &amp;lt; 2/3 of pts with HER2-negative mBC in our study were gBRCAm tested from 2020 onwards. gBRCAm testing was lower in pts with HR+ disease and was performed at a later timepoint for pts with de novo disease. Wider and timelier implementation of gBRCAm testing to identify pts that could benefit from PARPi is warranted. Fewer pts with gBRCAm who had HR+ tumors or de novo disease received PARPi than pts with TNBC. Our data suggest that pts who initiated PARPi had numerically longer OS than PARPi non-initiators; further research into OS trends and PARPi use in gBRCAm mBC would be of interest. Editorial acknowledgment: Medical writing assistance was provided by Leigh-Ann Booth, Ph.D. from BOLDSCIENCE Inc., funded by AstraZeneca and Merck Sharp &amp; Dohme LLC, a subsidiary of Merck &amp; Co., Inc., Rahway, NJ, US Legal entity responsible for the study: AstraZeneca. Funding: This study was supported by AstraZeneca and Merck Sharp &amp; Dohme LLC, a subsidiary of Merck &amp; Co., Inc., Rahway, NJ, US, who are codeveloping olaparib. Table. gBRCAm testing rates over time in pts with HER2-negative mBC HER2-negative mBC is defined as IHC 0, or 1-positive, or IHC2-positive/ISH-negative. *Olaparib approved in mBC; †Olaparib approved in eBC. eBC, early breast cancer; gBRCAm, germline breast cancer gene mutation; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC, immunohistochemistry; ISH, in situ hybridization; mBC, metastatic breast cancer; pt, patient; TNBC, triple-negative breast cancer. Citation Format: Siddhartha Yadav, Sam Hillman, Linlin Luo, Weiyan Li, Jagadeswara Earla, Xiaoqing Xu. BRCA testing and PARP inhibitor utilization in real-world HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS04-02.

Salvage Ablative Radiotherapy for Isolated Local Recurrence of Pancreatic Adenocarcinoma following Definitive Surgery.

Introduction: The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume. Methods: We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98-100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan-Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan. Results: Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37-87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6-71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26-56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46-72%) and 22% (95%CI, 14-37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17-40%) and 36% (95%CI 24-48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3-4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively. Conclusions: Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease.

Thoracic Reirradiation with Stereotactic Body Radiation Therapy (SBRT) for Recurrent Advanced Non-Small Cell Lung Cancer (NSCLC)

BackgroundNon-small cell lung cancer (NSCLC) local control remains suboptimal with rates around 75%. Stereotactic body radiation therapy (SBRT) is an option for isolated local recurrences of small volume recurrences. This study investigates the safety and efficacy of 60 Gy in eight fractions in large volume local recurrences. MethodsA retrospective chart review of patients treated with salvage SBRT for NSCLC lung parenchymal recurrence between July 2013 and February 2020. Reirradiation prescribed dose was 60 Gy in eight fractions utilizing SBRT technique. The primary endpoint was local control at most recent follow-up or death. Secondary endpoints included overall survival, disease-free interval, cancer-specific survival, and treatment related toxicities. ResultsSeven patients met criteria. Median follow up time was 38 months (18.1-72.4). Median age was 67 years (63-80). The median time to reirradiation was 18.2 months (7.3-28.6). Retreatment median ITV was 57.9cc (15.8-344.6) and PTV median was 113.6cc (38.3-506.9). Local control was maintained in four of seven patients (57.1%). Two of the seven patients (28.6%) remained alive. Median disease-free interval was 22.5 months (11-65). Three of seven patients (42.9%) had grade two toxicities. One patient (14.3%) had a grade 3 rib/chest wall toxicity with concurrent disease recurrence invading the chest wall. ConclusionThis study reports that SBRT of 60 Gy in eight fractions was delivered safely and effectively to large volume recurrent NSCLC previously treated with radiation therapy. The disease-free interval of nearly 2 years is meaningful for patients’ quality of life and duration of time off of systemic therapy.

Solitary Fibrous Tumours of the Orbit - Clinical Pathology, Therapy and Prognosis.

Solitary fibrous tumours are rare. The aim of this study is to describe the clinical features, therapy and outcome of affected patients and to identify factors associated with recurrence. Retrospective study of a cohort of 20 patients who underwent surgery for orbital solitary fibrous tumour at the University Department of Oral and Maxillofacial Surgery between 2002 and 2023. Demographic, clinical, and therapeutic data as well as tumour follow-up results were collected. Tumour volume and molecular genetic mutations were retrospectively determined. The median patient age was 49.5 years at initial surgery. The left orbit was affected in 65% of cases. The most common clinical symptom was proptosis (80%). This was reported with a mean lateral difference of 3.9 mm (range: 1 - 10 mm). The tumours were localised predominantly in the intra- and extraconal space, craniolateral quadrant and middle third. The median tumour volume was 7.66 cm³ (range 2.15 - 12.57 cm³). In all patients, the diagnosis was made by pathological examination. All tumours investigated showed a NAB2-STAT6 mutation. The most frequently detected mutation was the fusion NAB2 exon 4 - STAT6 exon 2. All patients were initially managed with frontolateral orbitotomy. Incomplete resection (R1-status) occurred in 35% (n = 7). The recurrence rate was 25% (n = 5), with a median disease-free interval of 45.5 months (range 23 - 130). 80% (n = 4) of recurrences were initially R1-resected. Orbital solitary fibrous tumours are rare tumours and are clinically manifested by signs of displacement of orbital structures. Diagnosis is made by histology and immunohistochemistry and can be proven with the molecular genetic detection of the NAB2-STAT6 mutation. The therapy of choice is complete surgical resection. R1-resection is more likely in the intraconal location as well as in location in the posterior third of the orbit - due to difficult surgical accessibility. The greatest risk factor for the development of recurrence is incomplete surgical excision. Late recurrences are possible, which is why a long-term connection to a specialised clinic is necessary.

PATH-10. SURGICALLY RESECTED RECURRENT DIFFUSE GLIOMAS: HISTOMOLECULAR SPECTRUM

Abstract Histological treatment-related changes (TRC) may mimic radiological progression in diffuse-gliomas on follow-up after complete therapy. If scans suggest recurrence, patients undergo re-surgery&amp; re-RT, if recurrence is histologically confirmed. We evaluated 1) baseline characteristics of surgically-resected gliomas re-operated for clinicoradiological suspected recurrence; 2) compared histological changes from initial surgery. All adult-type diffuse-gliomas (n=122) re-operated following complete therapy, with available initial&amp; subsequent slides reviewed, classified as per current WHO classification. Clinico-pathological features noted. RESULTS: Baseline median age:36years (IQR:29-44years), M:F=2.21, tumor-bed recurrence in majority (116/122). Of 92 astrocytomas, 47 were IDH-mutant (grade-2:18, grade-3:14, grade-4:15); 31 were IDH-WT (histological grade-2:4, grade-3:5, grade-4:22), IDH not-available (NA) in 14. Among IDH-mutant, 26 were MGMT-methylated (MGMT-M), 11 unmethylated (MGMT-UM). In IDH-WT 4 were MGMT-M, 23 MGMT-UM. Of 30 oligodendrogliomas, 21 were grade-2, 9 grade-3. All grade-2 gliomas (25astrocytoma, 21oligodendroglioma) showed high-grade transformation at re-surgery, with 40% astrocytoma upgrading to grade-3; 60% to grade-4. Six grade-3 astrocytoma recurred at same grade, while 18 as grade-4. Of 43 grade-4, on re-surgery 11 showed predominantly TRC ( &amp;gt;30%) with quiescent residual tumor (4 IDH-mutant, 5 IDH-WT, 2NA), while 32 showed recurrence (10 IDH-mutant, 18 IDH-WT, 4NA), of which 11 had scant (&amp;lt;5%) to focal (6-30%) TRC along-with actively proliferating tumor. Only 2 oligodendrogliomas showed TRC. Median disease-free interval (DFI) between both surgeries was significantly higher for oligodendroglioma (6.76years) than astrocytoma (3.59years, p-value&amp;lt; 0.001); for grade-2 (5.37years)&amp; grade-3 astrocytoma (5.19years) than grade-4 (2.85years, p-value&amp;lt; 0.001); grade-2 versus grade-3 oligodendroglioma (7.02years versus 4.91years, p-value 0.041), &amp;for MGMT-M versus MGMT-UM (5.17 versus 3.02years, p-value&amp;lt; 0.01). Significantly, median DFI was lower for grade-4 astrocytoma with TRC than without (2.34 versus 3.27years, p-value 0.015). CONCLUSIONS: Pseudo-progression gets confused with progression more commonly in high-grade gliomas than low-grade gliomas, and is associated with surgery closer to therapy completion. Careful histological assessment thus may help guide management.

Single high-dose radiation therapy and liquid fiducial markers can be used in dogs with incompletely resected soft tissue sarcomas.

To evaluate the outcome and effects of single high-dose radiation therapy with the aid of liquid fiducial markers in dogs following resection of soft tissue sarcomas (STSs). 36 client-owned dogs. Dogs with a histologic diagnosis of a grade II or III STS that underwent liquid fiducial guided single fraction, 20-Gy stereotactic radiation therapy following surgical excision of an STS between May 2017 and March 2019 were prospectively enrolled in this study. Data collected from the medical records included patient signalment, tumor-related information, treatment details, and outcome. Kaplan-Meier survival analysis was performed for overall survival time (OST) and disease-free interval (DFI). The median OST and DFI were not reached, so restricted mean OST and DFI were also calculated. 36 dogs were included in the study. All dogs underwent radiation therapy a mean of 36.1 days (range, 20 to 59 days) after surgery. Acute and delayed radiation toxicity effects occurred in 80.5% and 36.1% of dogs, respectively, all of which affected the skin. Tumor recurrence was noted in 24.3% of dogs with a median time to recurrence of 272 days (range, 14 to 843 days). The restricted mean OST was 1,556 days (range, 1,383 to 1,728 days) and restricted mean DFI was 1,330 days (range, 1,101 to 1,559 days). The results of this study showed that administering a single 20-Gy fraction of radiation in combination with a liquid fiducial marker to treat marginally or incompletely resected STS in the absence of gross disease resulted in similar OST and DFI compared to other previously reported radiation protocols.

Surgical and oncologic outcomes in dogs with malignant peripheral nerve sheath tumours arising from the brachial or lumbosacral plexus.

Malignant peripheral nerve sheath tumours (MPNST) of a plexus nerve or nerve root cause significant morbidity and present a treatment challenge. The surgical approach can be complex and information is lacking on outcomes. The objective of this study was to describe surgical complication rates and oncologic outcomes for canine MPNST of the brachial or lumbosacral plexus. Dogs treated for a naïve MPNST with amputation/hemipelvectomy with or without a laminectomy were retrospectively analysed. Oncologic outcomes were disease free interval (DFI), overall survival (OS), and 1- and 2-year survival rates. Thirty dogs were included. The surgery performed was amputation alone in 17 cases (57%), and amputation/hemipelvectomy with laminectomy in 13 cases (43%). Four dogs (13%) had an intraoperative complication, while 11 dogs (37%) had postoperative complications. Histologic margins were reported as R0 in 12 dogs (40%), R1 in 12 dogs (40%), and R2 in five dogs (17%). No association was found between histologic grade and margin nor extent of surgical approach and margin. Thirteen dogs (46%) had recurrence. The median DFI was 511 days (95% CI: 140-882 days). The median disease specific OST was 570 days (95% CI: 467-673 days) with 1- and 2-year survival rates of 82% and 22% respectively. No variables were significantly associated with recurrence, DFI, or disease specific OST. These data show surgical treatment of plexus MPNST was associated with a high intra- and postoperative complication rate but relatively good disease outcomes. This information can guide clinicians in surgical risk management and owner communication regarding realistic outcomes and complications.

Prolonged 14-day continuous infusion of high-dose ifosfamide (14IFO) for relapsed/refractory high-grade osteosarcoma (R/R HOS): A retrospective multicenter cohort study.

11534 Background: The prognosis of patients (pts) with relapsed/refractory (R/R) High-Grade Osteosarcoma (HOS) remains dismal without an agreement on systemic therapy. The use of 14IFO with an external pump in outpatient setting (1g/sqm/day x 14 days every 21) in R/R HOS pts is limited. This is the first retrospective cohort study focused on 14IFO activity and toxicity in this setting (NCT04651569). Methods: Five Centers of the Italian Association of Pediatric Onco-Hematology and Italian Sarcoma Group participated to the study. Primary aim is to investigate 14IFO activity in pts with R/R HOS younger than 40 years. Secondary aim is to evaluate toxicity, according to CTCAE v.5, and clinical benefit. Progression Free Survival (PFS) and Overall Survival (OS) analysis are performed using the Kaplan Meier method with 95% confidence interval (CI). Results: Between 2012 and 2021, 26 R/R HOS pts were treated with 14IFO (median follow-up: 17,5 months, range: 4,6 – 83 months). Median age is 19 years at the beginning of 14IFO; eleven pts (42%) are ≤ 18 years. Three pts (12%) have a localized HOS, twelve pts (46%) have pulmonary disease only and eleven pts (42%) have a pluri-metastatic HOS. Eleven pts (42%) have a relapsed HOS with a median disease-free interval (DFI) of 13 months before 14IFO, the remaining (58%) have a refractory disease to two or more treatments. Overall, thirteen pts (50%) receive 14IFO as second line therapy and fifteen pts (57%) are pre-treated with Ifosfamide in first line. Disease Control Rate is 57,5% (5 Partial Response + 10 Stable Disease). Seven pts (27%) receive a local treatment after 14IFO (5 surgery, 1 Radiotherapy (Rt), 1 Carbon Ion Rt). The median PFS is 4,1 months (95% CI 2.13, 7.37). 6-month and 1-year PFS are 38% (95% CI 24-63) and 8% (95% CI 2-29), respectively. The median OS is 13.7 months (95% CI 10.6 – 23.7). 1-year and 2-year OS are 51% (95% CI 35-75) and 22% (95% CI 9.5-49), respectively. Relapsed pts have both longer median PFS and OS compared to pts with a refractory disease [PFS: 7.33 months vs 2.13 months (p = 0.02); OS: 19.4 months vs 10.7 months (p = 0.1)]. Sixteen pts (61%) receive at least 4 cycles and an amount of 101 cycles are evaluated for toxicity. Grade 4 hematological toxicity is reported in 15 cycles (14,8%) as follows: i) white-blood cell decrease in 6 cycles (6%); ii) neutropenia in 7 cycles (7%); iii) thrombocytopenia in 2 cycles (2%). One patient has one episode of febrile neutropenia. No grade 3-4 non hematological toxicities are reported. Conclusions: This trial shows a non inferiority activity of 14IFO compared to other treatments in this setting, despite the small number of pts. Therefore, 14IFO should be considered as a treatment option in R/R HOS, especially for its well tolerated toxicity profile and the home-administration that improve patient’s quality of life and it could significantly reduce cancer care cost. Clinical trial information: NCT04651569 .

Anal carcinoma: A retrospective analysis in a Mexican cohort.

e15502 Background: Anal carcinoma is a rare neoplasm, representing &lt; 1% of all neoplasms with rising incidence and mortality. More than 90% of cases are linked with high-risk human papillomavirus (HPV). Other factors such as HIV status, smoking and socioeconomic disparity may have important roles. Few data are available on the Mexican population. Methods: Retrospective analysis of patients with pathology-confirmed anal carcinoma treated at an Oncology Reference Center in North-East Mexico from 2010 to 2020. Using descriptive statistics, we report clinical and pathological features, time from symptom onset to diagnosis and treatment, as well as response and recurrence rate. Results: Forty-one patients were included in the final analysis. The mean age at diagnosis was 61.4 +/- 13.8 years and 58.5% were women. Smoking history was identified in 17 patients (41.5%). 9.8% were HIV-positive, however 63.4% of all patients had unknown status at cancer diagnosis. Mean duration of symptoms to diagnosis was 344 days (range 4-1435 days) and the median interval from symptom onset to registration for oncology consultation was 424 days (range 28-1695 days). Patients attended a median of 3 (range 1 to 7) previous clinical consultations before being referred to our center. It is noteworthy that 44% of patients had hemorrhoidal disease history. Squamous cell carcinoma was the most common histological subtype with 93% of all cases, arising from the anal canal in 78% of cases, while 22% corresponded to perianal cancer. Regarding the clinical stage at presentation, 2.4% of patients had localized disease, while 95% had regional spread and 2.4% presented with distant metastases at diagnosis. Treatment intent was curative in 85.4%. Treatment modalities included radiotherapy (97%), surgery (7%), chemotherapy (88%). Concurrent chemoradiotherapy was received by 85%. Most patients were treated with a total dose between 45 and 60 Gy to the tumor volume. Radiotherapy delays due to toxicity occurred in 31.7% of cases, these unplanned treatment interruptions correlated negatively with response rate (p &lt; 0.001). The chemotherapy regimen used was 5-fluorouracil (5-FU) with mitomycin C (MMC) in 29%, capecitabine monotherapy in 31.7%, 5-FU with cisplatin in 12.5%, capecitabine with MMC in 5%, and capecitabine with cisplatin in 5%. Among patients treated with curative-intent, 46% had a complete response and 37% had a partial response. Relapse occurred in 10 cases (24%), the majority being local relapses (54%). Distant relapse occurred in 15% of all cases. The median disease-free interval (DFI) was 32.5 months (range 0-252 mo). Colostomy rate was 29%, the median colostomy-free survival (CFS) was 10 months (range 3-15 mo). The comparative analysis between MMC-based chemotherapy and chemo without MMC did not show difference in response rate, recurrence, DFS and CFS. Conclusions: Due to its rarity and complex management patients with anal carcinoma should be treated at experienced centers.