Curative Intent Research Articles

Effect of circulating tumor cells (CTC) and CTC clusters with PD-L1 dynamic biomarker on cellular burden in patients with ovarian cancer.

e17566 Background: In the precision oncology era, monitoring response to the treatments using circulating blood-based biomarkers e.g. circulating tumor DNA (ctDNA) and Circulating Tumor Cells (CTCs) are being rapidly evaluated and established. The leading cause of ovarian cancer patient mortality is owing to the delayed diagnosis, inability of patient selection for targeted therapies, including the use of immune checkpoint blockade (ICB) agents. The treatment of ovarian cancer usually involves a combination of surgery and chemotherapy. However, post operative resection and therapy with curative intent often fails in accounting the Minimal Cellular Disease (MCD). The dissemination of Circulating Tumor Cells (CTC) remains a dogma of Minimal Residual Disease (MRD) that diffuse and cause micro-metastasis through their epithelial to mesenchymal transitions (EMT) and ‘bio-mechanistic activation’ in blood circulation. Simultaneous detection of over-expression of Programmed Cell Death-Ligand 1 (PD-L1) on CTCs as a dynamic biomarker may be expedient for assessing patients for immune checkpoint inhibitor (ICT) therapy. Methods: In retrospective analysis of real-world data, 75 ovarian cancer patient’s peripheral blood was analyzed for the presence of CTCs with and without the expression of PD-L1 and CTC clusters. CTC were positively detected using OncoDiscover platform approved by CDSCO in 1.5 ml peripheral blood. The platform is multifunctional magneto nanosystem mediated by anti-epithelial cellular adhesion molecule (EpCAM) antibody. CTCs were identified as positive if they were EpCAM +ve, CK+ve, PD-L1 +ve, DAPI +ve and CD45-ve. PD-L1 expression on the CTCs was analyzed based on the linear intensity gradients of the fluorescence signals using image acquisition on an automated Zeiss Microscope. Results: At baseline sample analysis, 86 % (n=65) of the patients showed ≥ 1CTCs per 1.5 ml of blood. The CTC distribution in this study ranged from 1-9 CTCs. Whereas, 46.15 % (n=30) patients with CTCs showed the expression of PD-L1. Noteworthy, the highest number of CTCs were observed ~ 26.7 % (n=23) in age group 41-50. Interestingly, 8 % (n=6) of total patients showed the presence of CTC clusters. The presence of CTCs with expression of PD-L1 and CTC clusters did not correlate with factors like staging, follow ups, metastasis, and DFS status. Conclusions: We observed presence of MCD and MRD in CRC patients, in spite of curative intent in ovarian cancers. Detection of CTCs, CTC clusters with over-expression of PD-L1- as a real time dynamic biomarker may be useful for assessing the patients for early metastasis, regression, and selecting patient suitable for immune checkpoint inhibitor (ICT) therapy when the tissue is inadequate or unavailable for better outcome.

Fractionated external-beam radiation therapy in elderly patients.

e13764 Background: To review the outcome of elderly patients treated with fractionated external-beam radiation therapy (RT) at a privately-owned, multi-disciplinary cancer center. Methods: From January 7, 2019, to August 22, 2023, 63 elderly patients were treated with fractionated RT at California Cancer Associates for Research and Excellence (“cCARE”), a privately-owned, multi-disciplinary cancer center in Fresno, California. The median age at the time of RT was 90 y/o (range, 85-98 y/o). Twenty-three patients were female and 40 were male. Forty-six patients identified as white and 17 as non-white. Treatment sites/histologies included primary lung 10, non-melanomatous skin 6, bone metastases 6, breast 5, esophagus 5, H&N 5, prostate 4, primary CNS 3, brain metastases 3, rectum 3, bladder 2, Merkel tumor 2, sarcoma 2, anus 1, liver 1, melanoma 1, multiple myeloma 1, NHL 1, pancreas 1 and stomach 1. Results: Thirty-two of the patients (51%) were treated with curative intent. The remaining 31 patients were treated for palliation. All patients were treated with fractionated RT. However, 4 patients also received a separate course of single-fraction RT. Twenty-seven patients received more than one course of RT. The median RT course was 10 fractions (range, 1-35 fractions). Most patients had previously been treated with systemic therapy. Nearly one third (31%) received systemic therapy concurrent with their RT. The majority of the patients (73%) completed their prescribed course(s) of RT. Many patients (61%) required one or more treatment breaks. The median duration of a treatment break was 1 day (range, 1-29 days). There were no grade 3 or higher RT toxicities recorded. The median follow-up since RT was 5 months (range, 1-59 months). Twenty-four patients have expired. The mediation duration from RT to death was 5 months (range, 1-32 months ). Of the remaining 39 patients, 92% were scored as clinically stable at the time of their last f/u visit. Conclusions: In our experience at cCARE, fractionated RT was administered to elderly patients and the majority completed their prescribed treatment courses. None of the patients in our review experienced clinically significant side effects (Grade 3 or higher) during their RT even in the cohort (31%) who were treated with concurrent systemic therapy. Clearly, careful patient selection and state-of-the-art RT administration is paramount. It is also highly advantageous for patients to be treated in a multi-disciplinary setting such as cCARE where seamless coordination of cancer care among radiation oncologists, medical oncologists and surgeons excels. A companion study is in process comparing the outcome of similarly matched elderly patients from our center who were treated with systemic therapy alone. We anxiously await the outcome of this vital comparison review.

Adjuvant immunotherapy and targeted therapy in early and locally advanced resectable lung cancer: expanding treatment tentacles?

Adjuvant platinum-based chemotherapy has been the main treatment following surgical resection with curative intent in early and locally advanced nonsmall cell lung cancer (NSCLC) albeit with a 5% improvement in 5-year survival rates. Recent advances in biomarkers pave the way for targeted treatments and immunotherapy in a broader spectrum of patients with subsequently improved clinical outcomes. Targeted treatments and immunotherapy have established their place in the adjuvant setting of resected NSCLC.

Effect of circulating tumor cells in clinically stable patients on the conundrum of recurrence with cellular residual disease.

e15040 Background: Despite no evidence of disease by radiological imaging, up to 30% breast cancer cases are known to relapse after treatment with a curative intent. The presence of CTCs in stage I-II cancer patients signals the activation of extravasation and invasion process leading to micro-metastasis and may lead to poor outcome. CTCs in blood circulation at any stage of cancer indicate detectable Minimal Cellular Disease (MCD). Thus the longitudinal investigation of patients with such biomarker remains highly implicative to predict the recurrence, therapy escalations, and dose modifications. The expression of Program Death - Ligand 1 (PD-L1) on CTCs is a dynamic biomarker and they may escape the elimination by immune system, indicative of progression of metastatic signature. Methods: Retrospectively, ina cohort of 20 cancer patients (e.g. lung, colon-rectal, breast, stomach, etc.) who recently underwent treatment were investigated for the presence of CTCs using CDSCO approved OncoDiscover platform having multi-components conjugated with anti EpCam antibody on magnetic nanoparticles. All patients represented clinically stable disease from previous radiological findings. CTCs enumeration assay was performed using CD45, EpCAM+, and CK18 and over-expression of PD-L1 in1.5 ml of peripheral blood using automated motorized Zeiss fluorescence microscopy. Results: In spite of 'no radiological' findings with clinically stable disease, out of 20 selected patients, 75% (n=15) showed at least 1 CTC. While, 55% (n=11) patients were detected with 1 CTC, 5% patients (n=1) with 2 CTCs, and 15% patients (n=3) were identified with 3 CTCs. In addition, 50% (n=10) of patients demonstrated with PD-L1 expression on CTCs; 1 patient exhibited a CTC cluster. Conclusions: Patients showed CRD in spite of a stable disease, which is an indication of progression of localized disease transforming from primary to secondary. The longitudinal monitoring of patients for CTCs with PD-L1 expression may reveal ‘real time’ residual disease, progression, regression, and actual response to the treatment. CRD monitoring can improve the curative intent by improving PFS and OS in solid cancers.

Cisplatin and capecitabine as definitive chemoradiation for squamous cell carcinoma of the anal canal (SCCAC): A prospective cohort.

e15503 Background: SCCAC is a rare disease. The standard of care treatment with curative intent is chemoradiation (CRT) with mitomycin (MMC) or cisplatin (CDDP) plus infusional 5-Fluoracil (5-FU). Capecitabine may replace 5-FU in MMC doublet. However, MMC and infusional pumps are frequently unavailable in underdeveloped countries. CCDP and capecitabine are widely available, but there is no prospective data about the feasibility and efficacy of this combination in a definitive SCCAC CRT setting. Methods: A Prospective cohort study aimed to evaluate the safety and efficacy of treatment with chemoradiation with CDDP 60mg/m2 D1 and D29 plus Capecitabine 825mg/m2 BID in a population without MMC and infusional pump access. Eligible patients (pts) had T2-4, N0-3, and M0 disease candidates for a full curative CRT regimen. The study data were prospectively collected using REDCap. The primary endpoint was the response by RECIST v.1.1 at 24 weeks(w). The secondary endpoints included toxicity by CTCAE v.5.0, adherence, PFS, and OS. Results: We enrolled 40 consecutive pts between Aug/2019-Dec/2022 in a tertiary cancer center in Brazil. The median age was 61y, the majority were stage III (n = 31, 77.5%) and ECOG 1 (n = 20, 50%). HIV+ serology was observed in 11 pts (27,5%). All patients received CRT, with a median dose of 54Gy in the primary tumor and 45Gy in the elective nodes. At 8w, 35% (n = 14) had a complete response (CR), 50% (n = 20) partial response (PR), and 2.5% (n = 1) progressive disease (PD). At 6 months, CR was observed in 55% (n = 22), PR in 22.5% (n = 9), and PD in 10% (n = 4). 11 pts had disease recurrence, and six died. 1y OS was 94.7% (IC95%: 80.7- 98.6%), and 1y PFS was 75.3% (IC95%:57.8 - 86.3%). Colostomy-free survival at one year was 89.6% (IC95%: 74.7 - 95.9%). Median PFS and OS were not reached with a 2-year median follow-up. Regarding toxicities, radiodermatitis was observed in 94% (n = 36), nausea in 90% (n = 36), and diarrhea in 65% (n = 26). Any grade 3/4 toxicity was present in 27.5% (n = 11), being the majority of radiodermatitis. Four older pts (average age 73y) had definitive suspension of treatment due to toxicity, 06 pts were hospitalized because of a skin infection, and one died due to treatment toxicity. Conclusions: Definitive chemoradiotherapy with cisplatin and capecitabine is feasible; however, older populations require extra attention to early toxicities management.

VELOCITY-Lung substudy-03: A phase 2 study of neoadjuvant domvanalimab (dom)+zimberelimab (zim)+chemotherapy (chemo) or zim+chemo followed by adjuvant dom+zim or zim in patients with resectable stage II-III non-small cell lung cancer (NSCLC).

TPS8121 Background: Management of resectable NSCLC involves surgery with perioperative systemic therapy. Immune checkpoint inhibitors (CPIs) and targeted therapies are now used in the perioperative setting, leading to improved survival outcomes. The combination of dom (anti–T-cell immunoglobulin and ITIM domain [TIGIT]) and zim (anti–programmed death protein 1 [PD-1]) has shown promising antitumor activity with a manageable safety profile in metastatic NSCLC and may provide an opportunity to improve clinical outcomes in the perioperative setting in early-stage, resectable NSCLC. Substudy-03 of the VELOCITY-Lung platform study is evaluating novel perioperative treatment combinations in patients with newly diagnosed, resectable, stage II-III NSCLC. Methods: VELOCITY-Lung (NCT05633667) is an open-label, multicenter, phase 2 platform study with 3 ongoing substudies targeting the different NSCLC patient populations. Key eligibility criteria for Substudy-03 include age ≥ 18 years, histologically/cytologically confirmed stage II, IIIA, IIIB (T[3-4]N2) (per AJCC 8th ed.) squamous or nonsquamous NSCLC considered resectable with curative intent, no prior systemic or CPI therapy or radiotherapy, ECOG PS 0-1, any PD-1 ligand (PD-L1) status, and no actionable EGFR or ALK genomic alterations in patients with nonsquamous NSCLC. Randomization in Substudy-03 will be stratified by disease stage (II vs III) and baseline PD-L1 expression status (≥ 50% vs < 50%). Current treatment groups in the neoadjuvant phase of the preliminary stage are: (A) dom+zim+platinum (Pt)-based chemo or (B) zim+Pt-based chemo for a maximum of 3 cycles; this will be followed by definitive surgery within 6 weeks of completing neoadjuvant treatment. Adjuvant treatment will include: (A) dom+zim or (B) zim and will begin within 12 weeks of surgery. Patients will continue to receive adjuvant treatment until disease recurrence, death, or unacceptable toxicity or to a maximum of 14 cycles. Dosing will be as follows: zim 360 mg intravenously (IV) once every 3 weeks (Q3W) and dom 1200 mg IV once Q3W (up to 3 cycles in the neoadjuvant phase and up to 14 cycles in the adjuvant phase). Pt-based chemo will be based on patient tumor histology (squamous vs nonsquamous). The primary endpoint is pathological complete response rate, defined as the percentage of patients with no residual invasive cancer in resected lung specimens and lymph nodes, assessed by local pathology review. Secondary endpoints include major pathological response rate (percentage of patients with ≤ 10% residual tumor in lung and lymph nodes at surgery), event-free survival, overall survival, and safety. Approximately 31 patients will be enrolled into each treatment group of the preliminary phase. The study is currently recruiting. Clinical trial information: NCT05633667 .

Evaluating the impact of socioeconomic status on patient satisfaction in radiation oncology.

e23166 Background: Patient satisfaction (PS) is a critical indicator in evaluating healthcare quality. While the impact of socioeconomic status (SES), on healthcare outcomes is well-documented, its specific connection to PS in the context of radiation oncology remains unclear. This study aims to delineate the correlation between SES, as determined by the Area Deprivation Index (ADI), and PS within our healthcare system. Methods: In this single institution study, National Research Council (NRC) PS survey questionnaires were prospectively collected from patients who visited 4 separate outpatient academic radiation oncology sites between May 2021 and November 2023. Area Deprivation Index (ADI) data for these patients was sourced from the Neighborhood Atlas, encompassing both national percentiles and state deciles, with higher values indicating a greater level of SES disadvantage. To assess the data, univariate (UVA) and multivariable (MVA) logistic regression analyses were performed on the survey's recommendation scores, which ranged from 0 to 10, with scores of 9 or higher suggesting a greater propensity to recommend the facility or provider. Results: Our analysis included 7,501 survey responses with a cohort that was majority female (55.3%), curative intent (81.5%), and had a breast cancer diagnosis (30.4%). Most survey responses were follow-up visits (69.0%). Mean state and national ADI scores were 3.94 and 50.75, respectively. The UVA revealed curative intent (OR 1.68, p < 0.001), follow-up visits (OR 1.69, p < 0.001), and breast cancer diagnosis (OR 1.42, p = 0.018) as predictors of higher likelihood to recommend the facility or the provider. Patients with a national ADI above the mean were less likely to recommend the facility (OR 0.81, p = 0.050) or the provider (OR 0.71, p = 0.002). The MVA, outlined in Table 1, showed the influence of national ADI on provider recommendations remained significant (OR 0.730, p = 0.005) but not for facility recommendations (OR 0.832, p = 0.089). All other variables remained significant on the MVA. Conclusions: Respondents experiencing greater SES disadvantage were significantly less likely to recommend their provider. These findings underscore the necessity of incorporating SES as a factor when evaluating PS. Further research is necessary to determine the root cause of the impact of SES on PS and to explore the complex dynamics of patient-provider interactions. [Table: see text]

Patient Experiences of Specialty Palliative Care in the Perioperative Period for Cancer Surgery

ContextThough patients undergoing treatment for upper gastrointestinal (GI) cancers frequently experience a range of sequelae and disease recurrence, patients often do not receive specialty palliative care soon after diagnosis and it is unknown in what ways they may benefit. ObjectivesTo understand patient experiences of specialty palliative care in the perioperative period for patients seeking curative intent upper GI oncologic surgery. MethodsAs part of a randomized controlled trial, we conducted in-depth interviews between November 2019 and July 2021 with 23 patients in the intervention arm who were undergoing curative intent treatment for upper GI cancers and who were also followed by the specialty palliative care team. ResultsWe found five themes that characterized patient experiences and perceptions of specialty palliative care. Patients typically had limited prior awareness of palliative care (theme 1), but during the study, came to understand it as a “talking” intervention (theme 2). Patients whose concerns aligned with palliative care described it as being impactful on their care (theme 3). However, most patients expressed a focus on cure from their cancer and less perceived relevance for integration of palliative care (theme 4). Integrating specialist palliative care practitioners with surgical teams made it difficult for some patients to identify how palliative care practitioners differed from other members of their care team (theme 5). ConclusionWhile receipt of specialty palliative care in the perioperative period was generally perceived positively and patients appreciated palliative care visits, they did not describe many needs typically met by palliative care practitioners. Trial Registrationclinicaltrials.gov registration: NCT03611309.

Tislelizumab plus tyrosine kinase inhibitor versus active surveillance in patients with ablated high-risk hepatocellular carcinoma: An open-label, parallel controlled, prospective cohort study.

e16238 Background: In IMbrave050, adjuvant atezolizumab plus bevacizumab demonstrated improvement in recurrence-free survival vs active surveillance in patients at high risk of hepatocellular carcinoma (HCC) recurrence following resection or ablation with curative intent. However, there is limited study on programmed cell death protein 1 (PD-1) inhibitor plus tyrosine kinase inhibitor (TKI) as postoperative adjuvant therapy for HCC. We aimed to assess the safety and efficacy of tislelizumab (a PD-1 inhibitor) plus TKI as adjuvant therapy versus active surveillance in patients at high risk of HCC recurrence after curative ablation. Methods: This study enrolled patients with HCC at high risk of recurrence following curative ablation. Patients were paralleled to Arm A (tislelizumab plus TKI) or Arm B (active surveillance). Patients in Arm A received tislelizumab (200 mg, IV, q3w) plus TKI for three months (4 cycles) following curative ablation, while those patients in Arm B underwent active surveillance. Primary endpoints were safety and tumor recurrence rate. Secondary endpoint was disease free survival (DFS). Exploratory endpoints included biomarkers related to the recurrence. Results: A total of 48 patients were enrolled with a median follow-up time of 283 days (IQR: 123-460 days, clinical cutoff date: 1 Jan 2024). Nine patients (37.5%) reported at least one adverse event of any degree in Arm A and three patients (12.5%) reported in arm B, most of which were mild. Only one patient in arm A experienced a grade 3 treatment-related adverse event, which improved after administration of symptomatic treatment. The recurrence rate of patients in arm A was 20.83%, which was significantly lower than the 58.3% in arm B (OR = 0.188 [95% CI: 0.052 - 0.674], P = 0.017). Four cycles of adjuvant tislelizumab plus TKI therapy was associated with significantly improved DFS (median, not evaluable [NE]) compared with active surveillance (median, 188 days [95% CI: 78.4 - 297.6 days]; HR = 0.396 [95% CI: 0161 - 0.973], P = 0.044). The absence of tislelizumab treatment (OR = 4.823 [95% CI: 1.091 - 21.329], P = 0.038) and multiple tumor lesions (OR = 7.651 [95% CI: 1.270 - 46.114], P = 0.026) were risk factors for recurrence of HCC after curative ablation. Conclusions: The safety of tislelizumab plus TKI combination therapy were generally manageable. Statistically significant and clinically meaningful improvement in tumor recurrence rate and DFS were seen in patients receiving combination therapy vs active surveillance. This study was a positive attempt to undergo short-course PD-1 inhibitor plus TKI combination therapy in patients with HCC at high risk of recurrence following curative ablation, showing promising efficacy in preventing HCC recurrence. Clinical trial information: NCT06059885 .

Emergency treatment for primary intracranial germ cell tumours (PICGCTs).

e17020 Background: PICGCTs arise de novo in children and young adults, most frequently in the pineal or suprasellar regions. Here, we evaluate the acute pathway for patients (pts) with PICGCTs managed at our Emergency Cancer Treatment Centre. Methods: Retrospective observational study from 1984-2022 at a single institution. Data was collected from paper and electronic patient records for all PICGCT pts, including pts treated with our intracranial regimen EP-OMB (Etoposide-Cisplatin alternating every week with Vincristine-Methotrexate-Bleomycin) administered with and without intrathecal Methotrexate. Results: To date, we have identified 43 pts with intracranial disease treated at our Centre over 38 years: 25 pts (58%) with PICGCT, 18pts (42%) with germ cell tumour brain metastases treated with EP-OMB and excluded from analysis. Most PICGCT pts are male (92%, n=23) with a median age 25 (range 17-50). The majority present with symptomatic disease (88%, n=22) confined to the pineal gland (72%, n=18), with hormone dysfunction in 24% ( n=6). Only two female pts (8%) have presented with suprasellar and pituitary midline lesions causing headache, progressive visual loss and hypothalamic failure including cranial diabetes insipidus. Eloquent areas in the brain cannot be biopsied so only 60% PICGCTs ( n=15) were confirmed histologically, 47% as germinoma ( n=7), 27% dysgerminoma ( n=4), 27% unclassified ( n=4). Tumour markers (TM) were elevated in all pts with cerebrospinal fluid (CSF) evaluation ( n=5) compared to elevated serum TM in under half (44%, n=12). 68% pts required emergency treatment for a new cancer diagnosis ( n=17): neurosurgery (59%, n=10), chemotherapy (35%, n=6) or radiotherapy (6%, n=1). 88% PICGCT pts received EP-OMB ( n=22) with intrathecal Methotrexate in 63% ( n=14). For all PICGCT pts, 72% pts remain alive ( n=18) with median follow-up 3.8 years (range 0.2-27.3). For 36% pts with TM relapse or radiological progression despite treatment ( n=9), 44.4% remain alive ( n=4) with median overall survival at 6.8 years (range 1.1-18.6). Conclusions: PICGCT pts frequently require emergency surgical treatment for a new cancer diagnosis. Although rare, accurate diagnosis will affect management and prognosis in this young patient group. CSF rather than serum TM analysis is crucial for diagnostic work-up. Consensus on optimal management is warranted given the potential toxicity from multiple therapeutic interventions administered with curative intent.

A randomized, double-blind, placebo-controlled phase II study of adjuvant pembrolizumab versus placebo in patients with head and neck squamous cell cancers at high risk for recurrence: The PATHWay study.

6008 Background: Anti-PD1 therapy has become an essential treatment in recurrent and metastatic head/neck squamous cell carcinoma (HNSCC). The optimal use of anti-PD1 therapy in the curative setting is not established. Understanding the benefits of adjuvant anti-PD1 treatment in high risk HNSCC patients treated with curative intent is necessary. Methods: The PATHWay trial (NCT02841748) is a multi-site, randomized, placebo (PL) controlled trial of pembrolizumab (IO) in patients following curative treatment of high recurrence risk HNSCC. Patients with AJCC 7th edition stage IVa, IVb, and select III HNSCC or multiple primaries were eligible if their cancers had an estimated > 40% chance of recurrence and were not eligible for additional therapy. Patients enrolled into six group criteria: A) high risk nodal disease or interrupted radiation treatment; B) salvage surgery including positive margin; C) Indeterminate distant lesions concerning for metastasis; D) Oligometastatic disease treated definitively; E) Microscopic residual disease after surgery; or F) Multiple prior recurrences or multiple treated primaries who have undergone surgery ≥ 2 times. Patients were randomized with stratification for HPV and EBV status, and received pembrolizumab 200mg IV or placebo for up to 18 cycles. The primary study endpoint was progression-free survival (PFS). The targeted sample size was N=100 patients (50 per arm), which provided >90% power to detect a hazard ratio (HR) of 0.45, based on a stratified logrank test at a one-sided alpha level of 0.10. Results: A total of n=49 IO and n=51 PL patients were enrolled between 2016 and 2023 across 10 US sites. Mean age was 62; 33% female; 45% nonsmoker; 20% HPV+, 2% EBV+. Cancers were stage III (24%), IVa (39%), IVb (8%), with prior surgery in 95% and prior RT in 78%. Median follow-up was 33 months. Compared to PL, IO treated patients had superior PFS with HR 0.61 (80% CI: 0.43-0.86, one-sided p=0.021). PFS rates for IO were 65% and 54% at 1 and 2 years, respectively compared to 48% and 33%, respectively for PL. Overall survival (OS) was not significantly different in IO vs. PL treatment (HR = 1.00, 80% CI: 0.6-1.68, p=0.45). IO improved PFS in 2 sub-groups: In post-salvage surgery patients (group B, n=37), IO had superior PFS vs. PL (HR 0.34, 80% CI: 0.18-0.67, p=0.016); In patients with multiple recurrences/primaries (group F, n=37) IO had superior PFS vs. PL (HR 0.48, 80% CI: 0.27-0.88, p=0.057). Adverse events between treatments were comparable, with 3 (6%) grade 4 adverse events in PL and 1 (2%) grade 5 (2%, unrelated) and 1 grade 4 (2%) in IO. Conclusions: Pembrolizumab treatment for 1 year in patients with high risk of recurrent HNSCC following curative therapy resulted in a statistically significant improvement in PFS compared to placebo, and the benefit was maintained in key subgroups. Clinical trial information: NCT02841748 .

Current management practices of de novo oligometastatic breast cancer: Real-world data from a physician survey.

1104 Background: De novo oligometastatic breast cancer (oligo-mBC) is generally defined as < 5 lesions at the time of diagnosis and represent a steadily increasing subset of metastatic cancers. Several retrospective studies demonstrated prolonged overall survival (OS) for select patients with oligo-mBC when treated with multimodality therapy (chemotherapy, surgery, and radiation). However, randomized trials that tested surgical resection of the primary tumor, or radiation of oligometastases (including recurrent and de novo disease) showed no OS benefit. No randomized trials to date have tested all 3 treatment modalities combined (as used with curative intent in early-stage disease). Current NCCN guidelines do not include specific recommendations for de novo oligo-mBC, the St Gallen International guidelines allow multimodality therapy for carefully selected patients. We surveyed practicing medical oncologists through the ASCO survey pool regarding their use of multimodality therapy in de novo oligo-mBC. Methods: An online survey was sent to the ASCO Research survey pool (N=999) between 11/14/23 – 12/29/23, 193 ASCO members completed the survey. Data was confidential and anonymous. Results: The majority (76-79%) of respondents recommend starting with palliative systemic chemotherapy. If patients have a response to initial chemotherapy, 42-54% recommend ablative radiation to all residual lesions, and 38-52% recommended surgical resection of the primary tumor. Overall, multimodality therapy is recommended sometimes by 29-36%, often by 19-29%, almost never by 32-41%, and never by 2-7% of respondents. Recommendations varied by disease subtype (Table). Conclusions: These survey data indicate varied practices in the treatment of de novo oligo-mBC. This highlights the need for future randomized clinical trials to investigate whether there may be survival benefit by receptor subtype in de novo oligo-mBC treated with curative intent multimodality therapy as used in locally advanced cancers. [Table: see text]

Patterns of progression in oligometastatic hormone receptor positive breast cancer after first-line systemic treatment at the metastatic stage.

e13054 Background: In recent years, thanks to large, consecutive and retrospective series, knowledge of oligometastatic breast cancer (OMBC) has improved. However, the underlying pathophysiological mechanisms and patterns of progression of OMBC remain largely unknown. The aim of this study is to determine whether the limited capacity of OMBC to metastasize persisted in patients receiving first-line systemic treatment at the OMBC stage. To obtain a biologically homogeneous cohort, the analysis focused on hormone receptor positive (HR+) OMBC. Methods: We retrospectively reviewed all patients consecutively diagnosed and treated from 2012 to 2020 at our institution for synchronous and metachronous HR+ OMBC. Included were HR+ MBC patients with up to five metastases at diagnosis with no other criteria. Clinical and biological characteristics at diagnosis of first metastases, types of treatment (local ablative treatment of all sites (LAT) vs palliative treatment), outcomes and patterns of progression after a first line systemic treatment at the oligometastatic stage were recorded. Progression-free survival (PFS) and overall survival (OS) rates with a 95% confidence interval were estimated using the Kaplan Meier method. Results: Out of 1,686 patients treated for MBC at our institution between 2012 and 2020, 11.0% (186/1,686) met inclusion criteria. Among these 186 HR+ OMBC patients, 62.2% had SBR grade I/II HR+, and 19.3% had HER2+ OMBC. 93.5% patients had only one organ invaded, and 88.2% patients had one to three metastases at diagnosis. 66.7% had bone metastases, 60.2% had bone-only metastases, 18.3% had visceral (lung or liver) metastases, 14.5% had lymph node metastases and 6.5% had brain metastases. 35.5% of patients were treated with a curative intent including systemic treatment plus LAT. After a median follow-up of 73.4 months (95%CI= [69.3-76.8]), median PFS and OS were respectively 31.6 months (95%CI= [23.7-37.4]) and 90.9 months (95%CI= [70.0-109.9]). Five years PFS and OS were respectively 32.6 % (95%CI= [25.5-39.9]) and 66.3% (95%CI= [58.4-73.1]). During this period, 64.0% (119/186) of HR+ OMBC patients presented disease progression. Among the latter, 74.1% showed spread with no more than five metastases (oligoprogression), and 82.6% in only one organ. 27.7% (33/119) of patients were able to benefit from LAT. Conclusions: HR+ OMBC incidence is 11%. Among patients with progressive HR+ OMBC following first-line systemic treatment at the oligometastatic stage, a large majority presented oligoprogression and a substantial proportion were able to be treated by local ablative therapy with a curative intent at the time of this progression. The limited capacity of HR+ OMBC to metastasize thus persisted after a first-line systemic treatment. This could be an argument in favor of physiopathological mechanisms specific to oligometastatic disease.

67P Relevance of local treatment with curative intent (LT) against metastatic colorectal cancer (mCRC): Findings of a retrospective cohort study at the Comprehensive Cancer Center Munich (CCC MunichLMU)

67P Relevance of local treatment with curative intent (LT) against metastatic colorectal cancer (mCRC): Findings of a retrospective cohort study at the Comprehensive Cancer Center Munich (CCC MunichLMU)

Implementing geriatric assessment for dose optimization of CDK 4/6 inhibitors in older breast cancer patients (IMPORTANT trial): A pragmatic randomized-controlled trial.

TPS1132 Background: Current evidence from both randomized trials and real-world evidence studies suggests that older patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer derive clinical benefit from the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy. However, a higher risk for adverse events due to CDK4/6 inhibitors among older patients is evident, leading to a trend of initiating CDK4/6 inhibitors at a lower dose in clinical practice, though without evidence. The aim of the present randomized trial is to investigate whether lower initial dose of CDK4/6 inhibitors combined with endocrine therapy is comparable to full dose in older patients with advanced HR+/HER2-breast cancer that are assessed as vulnerable/frail based on comprehensive geriatric assessment (CGA). Methods: We designed a multi-national, open-label, pragmatic randomized controlled trial with non-inferiority approach. Patients ≥70 years old with advanced HR+/HER2- breast cancer with no curative intention, no prior treatment in an advanced setting, and suitable to receive a combination of CDK4/6 inhibitors plus endocrine therapy according to treating physician, are eligible for study inclusion. After informed consent, included patients fill out a self-administered CGA tool and categorized accordingly to fit, vulnerable, or frail, depending on the number of impaired CGA domains. Fit patients receive full dose of CDK4/6 inhibitors and endocrine therapy whereas vulnerable/frail patients are randomized to either -1 level lower CDK4/6 inhibitor dose or full dose and endocrine therapy. The randomization is stratified by type of CDK 4/6 inhibitor, type of endocrine therapy, and level of vulnerability. The treating physician decides on the choice of CDK4/6 inhibitor (abemaciclib, ribociclib, palbociclib) and endocrine therapy (aromatase inhibitors, fulvestrant). The primary endpoint is time to treatment failure whereas secondary endpoints include overall treatment utility, progression-free survival, overall survival, time to chemotherapy initiation, toxicity, quality-of-life, time to quality-of-life deterioration and cost-effectiveness. The evaluation of disease progression, toxicity assessment, and the follow-up strategy resembles clinical practice to enhance the pragmatic design approach of IMPORTANT trial. The trial also enables a hybrid decentralized approach where the initial patient visit is in-person whereas the visits for efficacy and toxicity evaluation can be performed digitally according to local practices. In total, 495 patients are planned to be included to allow 346 vulnerable/frail patients to be randomized. Enrollment: The trial is open for recruitment since February 2024 with a recruitment period of 30 months. Clinical trial information: NCT06044623 .

Preliminary results correlating post-operative ctDNA status with disease-free survival in patients with stage II (high risk)/III colorectal cancer in the BNT000-001 epidemiology study.

3526 Background: Despite standard-of-care surgical resection and adjuvant chemotherapy (ACT), disease recurrence in patients (pts) with stage II or III colorectal cancer (CRC) remains high. Circulating tumor DNA (ctDNA) analysis post-surgery with curative intent may help to identify pts with minimal residual disease at risk for recurrence. We report preliminary results of the BNT000-001 study exploring the prevalence and prognostic value of ctDNA positivity post-surgery in pts with stage II (high-risk) / III CRC. Methods: The BNT000-001 (NCT04813627) epidemiological study is enrolling pts in US, Germany (including screening through the Colopredict registry study), Spain, and Belgium with resected high-risk (per NCCN guidelines) stage II / III CRC for longitudinal follow up of their ctDNA status post-surgery and ACT. The primary objective of the study is to estimate the prevalence of ctDNA positivity after surgery. Other objectives include evaluation of the prognostic value of ctDNA and identification of ctDNA positive pts who might be candidates for the interventional clinical trial BNT122-01 (NCT04486378). Disease-free survival (DFS) was measured from the post-surgery visit to disease recurrence/death and analyzed for all eligible pts who remain on study. ctDNA was analyzed using the laboratory developed AVENIO Oncology Assays (AOA) Surveillance test and reported as detected (“positive”), not detected (“negative”), or no result (“non-evaluable”). Results: 1094 pts have been screened, of which 874 pts were analyzed for post-surgery ctDNA status (data cutoff 15 Dec 2023). 142 pts were non-evaluable, resulting in 732 pts with defined ctDNA status. Prevalence of post-operative ctDNA positivity was 12.3% (90*/732). 87.7% (642/732) of pts were ctDNA negative. 826 pts were followed for the prognostic value of post-surgery ctDNA-positivity, excluding 48 ctDNA positive pts who transferred to the BNT122-01 treatment study. At a median follow-up time of 25.9 months, the median DFS of ctDNA positive pts was 12.16 months vs. median DFS not reached for ctDNA negative pts. The 12-month DFS rate was 55% for ctDNA positive vs. 92% for ctDNA negative pts. Of note, our analyses support the identification of ctDNA negative T4N2 pts as a high-risk group for recurrence. Post-surgery ctDNA positivity was associated with significantly increased risk for disease recurrence or death, with a hazard ratio of 10.2. Conclusions: This study supports existing evidence of the prognostic value of post-operative ctDNA in CRC pts. In ctDNA positive pts, the 12-month DFS rate was almost halved (55% vs. 92% in ctDNA negative). Clinical trial information: NCT04813627 . [Table: see text]

Personalized cell-free tumor DNA analysis for patients with HNSCC: Liquid biopsy for minimal residual disease detection in head and neck squamous cell carcinoma (LIONESS).

3010 Background: Early relapse and development of metastatic disease are some of the primary reasons for the poor prognosis of patients with head and neck squamous cell carcinoma (HNSCC). We conducted LIONESS, a single-center prospective cohort study to assess ctDNA in plasma and saliva from 76 patients with HNSCC receiving primary surgery with curative intent. Our objectives were to determine whether postoperative ctDNA detection can act as a biomarker for surgical tumor clearance and detection of molecular residual disease (MRD) and to evaluate the potential of tumor-informed ctDNA analysis for early molecular-level detection of relapse or prior to clinically confirmed recurrence. Methods: Plasma and saliva samples from 76 HNSCC patients (37% stage I/II, 63% stage III/IV; 93% p16-negative) were collected pre- and postoperatively and during clinical follow-up. Whole exome sequencing was performed on FFPE tumor tissue. Tumor-specific variants for personalized assay design (RaDaR, NeoGenomics Laboratories) were selected and used in the analysis of serial samples for evidence of MRD. ctDNA levels were correlated to tumor volumes from staging CT, as well as pathological and other clinical parameters. Results: 617 longitudinal plasma and 128 saliva samples were collected pre- and postoperatively and during clinical follow-up (median follow-up time of 805 days). In plasma, ctDNA was detected at a median estimated variant allele frequency (eVAF) of 0.036% (0.000327% - 18.43%). 34% of positive samples had ctDNA levels detected at an eVAF of ≤0.01%. Increased plasma ctDNA levels were detected postoperatively in 96% of cases with confirmed clinical recurrences (21/22) with a median lead time of 160 days (6 – 763 days). Of the remaining 54 patients with no clinically confirmed relapse, ctDNA was detected immediately postop in 7 of them. In 5 patients, adjuvant therapy resulted in persistent ctDNA clearance, while 2 patients are deceased. ctDNA was also detected in baseline saliva samples from patients with HNSCC of various anatomical locations with a 74% overlap with the corresponding plasma ctDNA profiles. There was a strong linear correlation between larger tumor volumes and higher eVAF and a trend towards higher eVAF in cases with regional and distant recurrences in comparison to local relapse. Pathological tumor stage and lymph node involvement were both strongly correlated with preoperative ctDNA shedding. Conclusions: The use of ctDNA detection in surgically treated patients with HNSCC has significant potential to guide treatment decisions, improve disease outcome and potentially spare patients unnecessary, partially invasive interventions during clinical follow-up. Our work demonstrates the feasibility of tumor-informed ctDNA assays for detection of MRD postoperatively and for monitoring for early detection of relapse.

Comparative genomic profiling of circulating tumor DNA and paired formalin-fixed paraffin-embedded (FFPE) DNA from Indian patients with breast cancer.

e14554 Background: Breast cancer (BC) is the most frequent malignancy and a leading cause of mortality in women worldwide. Although most BCs are treated with curative intent, 30-40 % patients experience disease progression or metastatic relapse. Considering high heterogeneity of BC, mutational profiling of solid biopsy may not be adequate for informed treatment decisions in all cases. Liquid biopsy based on circulating tumor DNA (ctDNA) analysis is emerging as an equivalent and alternative to tissue biopsy in clinical settings. Though extremely critical for management of BC, liquid biopsy is not a standard of care in India. Here we compared comprehensive genomic profiles of ctDNA and paired biopsy samples to determine the efficacy of ctDNA assay in detecting actionable mutational targets. Methods: Retrospectively, genomic DNA and matched ctDNA was isolated from both FFPE and blood samples of14 BC patients. The patients were confirmative with pathological findings, having metastatic infiltrating ductal carcinoma, or triple negative breast cancers. Genome-wide HRD, TMB and MSI scores based on the OncoIndx comprehensive gene panel (CGP) was determined. OncoIndx CGP targets 1080 cancer related genes along with 47 HRR genes and 1600 MSI signature sites. Libraries were prepared using a hybridization-capture method based on custom-designed OncoIndx 1080 CGP and sequenced (depth 5500 X) on Illumina Nextseq 2000 in a pair-end mode (150 x2). Variant calling was performed using a proprietary bioinformatics pipeline iCare. Results: All patients were diagnosed with metastatic infiltrating ductal carcinoma, or triple negative breast cancers. From the patient cohort, microsatellite instability (MSI) from ctDNA showed 100% concordance with FFPE DNA while tumor mutation burden (TMB) and homologous recombination deficiency (HRD) scores showed 71.4 % and 64.2 % concordance with FFPE DNA respectively. At the individual gene mutation level, the concordance TP53, BRCA1/2, PI3K family of genes, ESR1, PTEN, ERBB2, PALB2, and BRAF genes between ctDNA and FFPE DNA was 54.7%, 92.8%, 54.7%, 78.5%, 92.8%, 100%, 100%, and 100% respectively. Many important genomic alterations including PIK3CA:p.L334H, PIK3CA:p.E81K, ESR1:p.Q375L, BRCA2:p.X3040_splice, PTEN:p.D19H were exclusive to ctDNA thereby denoting potential tumor heterogeneities which could be missed from FFPE DNA. Conclusions: Our results suggest a high correlation between ctDNA and FFPE DNA detected by OncoIndx test in metastatic or triple negative breast cancer patients of Indian ethnicity. Although not a part of standard of care, liquid biopsy could be of significant potential for management of BC in the standard clinical settings. However, a thorough investigation of cancer stage, and clinical presentations are necessary to carefully evaluate the selection of ctDNA or FFPE DNA-based genomic profiling.

Outcomes for Patients With Head and Neck Sarcoma Treated Curatively With Radiation Therapy and Surgery

Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS. We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVAs) were conducted using Cox proportional hazards model. One hundred ninety-two patients had a median follow-up of 82 months. Tumors arose in the neck (n = 50, 26%), paranasal sinuses (n = 36, 19%), or face (n = 23, 12%). Most patients were treated with postoperative RT (n = 134, 70%). Postoperative RT doses were higher (median, 60 Gy; preoperative dose, 50 Gy; P < .001). Treatment sequence was not associated with LC (preoperative RT, 78% [63%-88%]; postoperative RT, 75% [66%-82%]; P = .48). On MVA, positive/uncertain margin was the only variable associated with LC (hazard ratio [HR], 2.54; 95% CI, 1.34-4.82; P = .004). LC was significant on MVA (HR, 4.48; 95% CI, 2.62-7.67; P < .001) for DSS. Patients who received postoperative RT were less likely to experience a major wound complication (7.5% vs 22.4%; HR, 0.28; 95% CI, 0.11-0.68; P = .005). There was no difference in the rate of late toxicities between patients who received preoperative or postoperative RT. H&N STS continues to have relatively poorer LC than STS of the trunk or extremities. We found LC to be associated with DSS. Timing of RT did not impact oncologic or long-term toxicity outcomes; however, preoperative RT did increase the chance of developing a major wound complication.

Effectiveness and toxicity of multidisciplinary treatment of head and neck cancer among people with HIV: Real-world evidence from a tertiary cancer center in Brazil.

e24139 Background: The incidence of head and neck squamous cell carcinoma (HNSCC) is rising among people with HIV (PWH). Previous studies have shown an increase in treatment-related toxicities in this population. This study aims to determine the demographics and treatment outcomes in this patient group at a tertiary cancer center in Brazil. Methods: HNSCC patients (pts) with HIV diagnosis treated at our institution between 2009 and 2022 were included. Medical charts were analyzed to extract clinical data. Log rank was used to compare survival estimates and stratified Cox regression model was used for univariate and multivariate analyses. Results: Our search identified 75 pts with HIV among 5956 pts with HNSCC. Median age at cancer diagnosis was 53 years (IQR 49-59.5), 80% were male and 82.7% had a smoking history. Most pts had an oropharynx primary tumor (38.7%) and locally advanced disease (80%), with T3 and T4 tumors in 55 pts (73.3%) and N+ in 48 pts (64.1%). A feeding tube (FT) was placed in 32% of pts before treatment. HIV viral load was detectable in 23 (30.7%) pts and 19 (25.3%) had a CD4 count of fewer than 200 cells/mm³, while 97.3% of the pts were on combination antiretroviral therapy at the time of HNSCC diagnosis. 26 pts were operated with curative intent and 20 pts received adjuvant therapy. In the total population, concurrent cisplatin-based chemoradiation (CCRT) was prescribed to 26 pts (34.7%) and 34 (45.3%) received radiotherapy (RT) alone. 65.4% of the pts in the CCRT group and 20.6% in the RT group were unable to complete treatment as prescribed, mostly due to toxicity. No pts with positive viral load or CD4 &lt; 200 cells/mm³ were able to complete CCRT. Treatment toxicity led to hospitalization in 24% of pts and 7 pts needed FT placement. There were 8 deaths during treatment, 5 in pts with CD4 &lt; 200 cells/mm³. Positive viral load was associated with CCRT interruption (p = 0.03) and a CD4 count of less than 200 cells/mm³ increased the risk of death during treatment (p = 0.02). Median overall survival (OS) was 31.7 months (IQR 14.6-53.7). Multivariate analysis did not show a statistically significant decrease in OS in pts with positive viral load or CD4 &lt; 200 cells/mm³. Factors associated with worse OS on multivariate analysis were FT usage (HR = 2.91; 95% CI: 1.45-5.83) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) greater than 1 (HR = 3.26; 95% CI: 1.46-7.24). Conclusions: HNSCC treatment in PWH is associated with a high discontinuation rate, even in pts with antiviral therapy. High toxicity rates and deaths during treatment were observed. Positive viral load and low CD4 count were considered contributing factors. ECOG-PS and enteral feeding tube usage were independently associated with worse survival. The development of more tailored strategies in this population is needed to improve outcomes in patients with HNSCC and HIV.