Neuroendocrine neoplasms (NENs) comprise a rare and heterogenous group of cancers, for which the role of radiation therapy continues to evolve. The purpose of this study is to analyze oncologic ...outcomes after the use of high-dose radiation in management of NENs at a tertiary hospital.
We performed a retrospective review of patients who received high-dose radiation with intent to cure or provide durable local control (defined as biologically effective dose (BED) ≥40, α/β = 10) for a localized or metastatic NEN from 2006 to 2019. Evaluation of disease status after radiation was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria when possible. Patients were grouped by differentiation (well-differentiated (WD) or poorly-differentiated (PD)) and stage (localized/locally advanced disease (L) or metastatic (M)) in analysis of probabilities of progression after radiation.
45 patients completed a radiation course with BED ≥40 for a NEN (median BED 72). With a median follow-up of 24 months after radiation, the 2-year actuarial rates of local relapse-free survival, new metastasis-free survival, progression-free survival, and overall survival after radiation were 98%, 45%, 41%, and 69%, respectively. 25 patients (56%) developed new metastases after completion of radiation, including 33% (n = 3) of patients with WD-L disease, 44% (n = 8) of WD-M, 77% (n = 10) of PD-L, and 80% (n = 4) of PD-M, with progressively shorter median times to progression (26, 9, 8, and 3 months, respectively; p = 0.093). Of the 25 patients evaluable by RECIST, 68% (n = 17) achieved either a complete or partial best response in the irradiated lesion.
These data suggest that focal, high-dose radiation has a role in the management of selected patients with NENs. Local failure is rare in patients with both well-differentiated and poorly-differentiated disease, although the predominant pattern of failure remains development of new metastases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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463
Background: Hepatocellular carcinoma (HCC) is an increasingly common and highly morbid malignancy worldwide, including the US. For early stage patients ablative strategies are ...important potentially curative treatment options. Stereotactic body radiotherapy (SBRT) has emerged as a promising non-surgical ablative therapy, although it is technically demanding and its comparison with radiofrequency ablation (RFA) remains confined to a single institution retrospective review. We queried the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to assess RFA and SBRT use in the US. Methods: We identified patients greater than 65 years old who were diagnosed from 2004-11 with stage I or II HCC and treated with RFA or SBRT. Survival analysis was conducted using Kaplan-Meier curves and log rank test. Factors associated with overall survival (OS) and early ( ≤ 90 day) hospital admission post-treatment were identified using propensity score (PS) adjusted multivariate analysis. Results: 825 patients were identified, 747 treated with RFA and 78 SBRT. 22 pts received both treatments and were excluded from this analysis. The mean Charlson comorbidity index was 1.0±1.1. Median age was 74, range 66-90. Patients who received RFA were more likely to live in the West and have liver decompensation. Patients who received SBRT were more likely to be white and treated in the Midwest. After using PS matching there were 78 in each cohort. In these patients, mean overall survival (OS) was 2.25 and 2.04 yrs for RFA and SBRT, p = 0.06. Younger age, lack of liver decompensation, treatment in the West, and liver transplantation were associated with longer OS, HR 0.96, p = 0.05; HR 0.37, p = 0.002; HR 0.57, p = 0.04; HR 0.18, p = 0.008, respectively. 90 day hospitalization rates did not differ between treatments; only liver decompensation was predictive of hospitalization, OR 3.33, p = 0.032. Conclusions: In a national cohort of early stage HCC patients, treatment with RFA vs SBRT resulted in no significant difference in OS. SBRT appears to be a comparable ablative strategy to RFA in this population. This highlights the need for a randomized trial comparing these two modalities.
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158
Background: Radiofrequency ablation (RFA) is a widely used local therapy for small, unresectable liver tumors (LT). Stereotactic body radiotherapy (SBRT) has been used for similar ...patients, and has the advantage that it can be used when lesions are adjacent to blood vessels, are difficult to reach and cannot be imaged on ultrasound. We examined RFA and SBRT outcomes for treating primary and metastatic LT at our institution and identified predictive factors for local control.
Methods: This study included 62 patients (pts) with 106 LT (69 metastatic, 37 primary) treated with SBRT and 127 pts with 206 LT (80 metastatic, 126 primary) treated with RFA from 2000 to 2010. 42 lesions were ablated intra-operatively while 164 were ablated percutaneously. Mean tumor size by maximum diameter was 2.2 cm (0.4-11) and 2.3 cm (0.6-6.2) for RFA- and SBRT-treated LT, respectively. Freedom from local progression (FFLP) for SBRT was defined as absence of progressive LT within or at the PTV margin while FFLP for RFA was defined as recurrence within or immediately adjacent to the ablation zone.
Results: With a median follow-up of 29.4 months (0.46 to 120.8), 1- and 2-yr FFLP rates for all SBRT- vs RFA-treated LT were 93% and 84% vs 86% and 83%. There were 14 cases of residual LT after RFA, 6 of which were re-ablated; these were not counted as RFA failures. Significantly more pts in the SBRT group had received prior systemic therapy (54% vs 31%, p=0.0001) and had active extrahepatic disease at treatment start (36% vs 23%, p=0.01). For SBRT, neither LT size nor dose predicted for FFLP. For RFA, tumor size ≥3 cm had worse FFLP (HR: 5.3, p<0.0001) but an intraoperative approach had better FFLP (HR: −2.2, p=0.01). For tumors >3cm, SBRT had significantly better FFLP than percutaneous RFA (HR: 0.32, p=0.018). In the RFA group, there were 9 complications, including pneumothorax, hemothorax, and small bowel injury, 2 of which resulted in death. In the SBRT group, there was 1 case of radiation-induced liver disease in a Child-Pugh Class B pt but no other significant toxicities.
Conclusions: SBRT is a safe alternative to RFA, can be used in a wider variety of patients, and may be more effective than percutaneous RFA at locally controlling larger liver tumors.
TPS630
Background: Hepatocellular Carcinoma (HCC) is among the most common types and leading causes of cancer death globally, and the incidence is on the rise. For patients with advanced ...hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICI) in combination with anti-angiogenic agents or other ICI improve survival compared with tyrosine kinase inhibition. Though ICI-based regimens can achieve prolonged responses in some patients and prolong overall survival, only a subset of patients achieve durable responses. There is an urgent need for strategies to overcome primary and acquired resistance. Many of these patients have symptomatic sites of disease which could benefit from local palliative radiotherapy. Radiotherapy also has the potential to elicit an abscopal immune response when combined with ICI. We hypothesize that combining Radiation Treatment (RT) with Durvalumab or the combination of Durvalumab + Tremelimumab (combination D+T in STRIDE regimen showed OS improvement in HIMALAYA trial in 1st line HCC) will achieve a meaningful response rate in advanced HCC patients after progression on other ICI-based therapies. Methods: This is an open label, single center, two-arm, non-comparative phase II trial. Key eligibility criteria are; histologically-diagnosed HCC with progression during or after prior PD-(L)1 checkpoint inhibitor immunotherapy and at least 1 RECIST 1.1-measurable tumor present which has not received RT or other local therapy prior to enrollment, ECOG 0-1, and Child Pugh score of A, B7, or B8. Patients are assigned sequentially to either single-agent durvalumab initiated starting 3 to 10 days after completing RT (25 Gy in 5 fractions to 1-5 sites of disease), at fixed dose of 1500 mg IV every 28 days, or a single fixed dose of tremelimumab of 300 mg IV administered on Day 1, initiated within 3-10 days of completing RT, in combination with durvalumab at fixed dose of 1500 mg IV every 28 days; for up to 24 months or until confirmed radiographic progression. The primary end point is overall response rate (ORR) and secondary endpoints include proportion of participants with adverse events, overall survival, progression free survival and duration of response. Exploratory endpoints include profiling of peripheral blood mononuclear cell immune cells and plasma biomarkers. We plan to accrue 30 patients to this study, 15 to each Arm, to evaluate ORR which would allow us to detect at least a 20% ORR, which would be a clinically meaningful improvement in efficacy in this population with otherwise poor treatment options assuming a statistical power of 87% and a directional 5% statistical significance level based upon an exact binomial test. The trial is open and enrolling. Clinical trial information: NCT04430452 .
TPS817
Background: Metastatic disease remains a consistent challenge for patients with gastrointestinal (GI) malignancies. Multiple immune checkpoint inhibitors (ICI) have been FDA approved for ...several GI indications. Still, patients will progress on these therapies, either immediately or after initial response. Palliative radiation therapy (RT) is an effective treatment that can be delivered to symptomatic metastases. It also has been reported to lead to an abscopal effect, which is an induction of response in a distant tumor. This is thought to result from increased tumor immunogenicity, tumor microenvironment modulation, and immune cell recruitment. Thus, palliative RT could not only relieve symptoms, but also potentially reinvigorate the immune response, prolong ICI efficacy, and delay next-line systemic therapy that carries risks of unknown efficacy and tolerability. Ongoing studies seek to elucidate prognostic and predictive biomarkers of the abscopal effect. However, cohorts of patients with GI malignancies are limited, so there remains a need for research in combining RT and immunotherapy in the context of metastatic GI cancer. ARM-GI aims to study the radiation-augmented immune response in patients with metastatic GI cancers progressing on immunotherapy. Methods: ARM-GI is a phase 2, single arm study. Key eligibility criteria include confirmed metastatic GI malignancy, progressive disease per RECIST v1.1 on any ICI, and at least 2 metastases, one of which can be safely left unirradiated. The target prescription dose is 30 Gy in 5 fractions to symptomatic sites through intensity modulated RT or stereotactic body RT. Patients will continue the same immunotherapy after RT and be evaluated per RECIST v1.1 longitudinally. The primary endpoint is overall response rate (ORR) per RECIST v1.1. Secondary endpoints include ORR per iRECIST, progression free survival, overall survival, local control in radiated lesion(s), effect of distant radiation on unirradiated target lesions, incidence of new metastatic lesions, safety by CTCAE v5.0, and time to new systemic therapy. The study will enroll 28 patients, with recruitment ongoing. Serial peripheral blood samples are collected for exploratory studies that will analyze for association with disease response and quantification of changes in circulating immune cell subsets after RT compared to baseline. Clinical trial information: NCT04221893 .
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616
Background: In this study, we analyze outcomes after the use of high-dose radiation therapy (RT) in management of neuroendocrine neoplasms (NENs) at a high-volume center. Methods: ...We performed a retrospective review of patients who received high-dose RT (defined as biologically effective dose (BED) >40, α/β = 10) for their NEN. Patients with small cell lung cancer and Merkel cell carcinoma were excluded, given their unique treatment paradigms. Results: 61 patients completed a radiation course with BED >40 for their NEN (median BED 70, range 44-180). Most tumors were gastroenteropancreatic in origin (n = 20); additional primary sites included lung (n = 11), head and neck (n = 10), cervix (n = 6), other (n = 9) and unknown (n = 5). 56% (n = 34) had well-differentiated (WD) neuroendocrine tumors, and 44% (n = 27) had poorly-differentiated (PD) neuroendocrine carcinomas. Disease stage at the time of RT was localized/locally advanced (LLA, n = 27), or metastatic/recurrent (MR, n = 34). The intent of RT was definitive (n = 18), post-operative (n = 10), for oligoprogression (n = 18), or purely palliative (n = 15). 48 patients had follow-up imaging at a median follow-up of 20 months after radiation. Outcomes were grouped by differentiation and stage, with median time to progression (mTTP) in months (Table). 8% of patients had local progression, while 44% developed new metastases, including 38% of WD-LLA, 47% of PD-LLA, 37% of WD-MR, and 67% of PD-MR disease with progressively shorter median time to progression (26, 10, 8, and 3 months, respectively). Conclusions: These data suggest that focal, high-dose radiation has a role in the management of NENs. Local failure is rare in patients with both WD-LLA and PD-LLA disease. The predominant pattern of failure is development of new metastases, which appear to occur sooner and more frequently in patients with PD and MR disease. Table: see text
5032
Background: Prostate specific membrane antigen (PSMA) and F-18-Fluciclovine PET imaging have high sensitivity for the detection of prostate cancer (PCa) metastases. MDT with stereotactic body ...radiation therapy (SBRT) to PET-detected Oligo PCa has been shown to improve progression free survival (PFS) and delay androgen deprivation therapy (ADT). However, in those patients (pts) who ultimately develop oligoprogressive disease following MDT, the utility of subsequent courses of MDT has not been well defined. Methods: A single institution retrospective review was undertaken to describe outcomes following ≥2 courses of PET-guided SBRT in pts with Oligo PCa. Pts included in this analysis had undergone initial SBRT for ≤5 PCa lesions detected on PSMA or Fluciclovine PET, and subsequently underwent ≥1 additional course of SBRT at progression. Baseline data collected included stage, PSA level, Gleason Score, tracer type, and concurrent systemic therapy. Endpoints collected for each SBRT course included PSA decline ≥50% (PSA50), PFS, and systemic therapy change free survival (RxFS) (initiation of ADT, or for pts already on ADT, addition of an androgen signaling inhibitor). Association of factors with PFS after SBRT2 were analyzed using multivariable Cox proportional-hazards models. Results: 34 pts underwent ≥2 courses of MDT (SBRT1, SBRT2). At SBRT2, progression was identified by PSMA-PET in 26 (77%) pts, and by Fluciclovine-PET in 8 (23%). With SBRT2, 18 (53%) had a concurrent systemic therapy change; 10 (29%) did not receive any systemic therapy. 12 pts subsequently underwent SBRT3. Progression was detected by PSMA PET in 9 (75%) and Fluciclovine PET in 3 (25%). Clinical outcomes are summarized in the table. In the multivariable analysis, predictors associated with PFS following SBRT2 were 1) PSA decline at SBRT1 (HR 1.10, 95% CI 1.05-1.16, P<0.001) and 2) PSA doubling time (PSADT) < 12 months at the time of SBRT2 (HR 11.52, 95% CI 1.36-97.38, P 0.025). Overall, from SBRT1 to last follow-up (median 25.2 months), 23 (68%) pts remained ADT-free (14 after SBRT2; 9 after SBRT3). Conclusions: Serial MDT for Oligo PCa detected on PSMA or Fluciclovine PET is feasible and results in PSA declines, independent of change in systemic therapy. There is a persistent but diminishing benefit of MDT over successive courses. Overall, 2/3 of pts were able to postpone the use of ADT. PSA decline at SBRT1 and PSADT at SBRT2 may be biomarkers for SBRT2 benefit. Despite the retrospective nature of this study and cohort heterogeneity, these data provide a rationale for serial SBRT in Oligo PCA, and the need for larger, prospective studies of this strategy. Table: see text
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442
Background: There are no formal guidelines for the management of GI cancer pts with lung-exclusive or lung-predominant metastases (LM), which generally take a more indolent course ...than metastatic disease occurring at other anatomic sites. We performed a retrospective analysis at a high-volume tertiary care center to evaluate host and tumor characteristics of this pt population, describe treatment approaches, and model patterns and rates of growth. Methods: Eligible pts were identified through Cancer Center registry data, provider recall, and electronic record review. Criteria included LM occurring either synchronously (SLM) or metachronously (MLM) w/primary cancer diagnosis; nodal, but not visceral or peritoneal, mets allowed. Data re: demographics, tumor characteristics, and rx modalities were collected. We reviewed all eligible CT +/- PET scan reports to gather data on #, location, and size of pulm mets, with all images subsequently reviewed by an independent radiologist. Up to 5 pulm mets were tracked through each pt’s clinical course. Growth rate was estimated using a linear mixed model analysis considering patients as the random. Results: Forty pts were identified between 9/2009 - 12/2019 (23 F/17 M; 28 white/7 Asian/5 other/multi; median age 62 y.o.; n = 15 w/tobacco hx). Tumor types: pancreatic (n = 18), colorectal (n = 12), hepatobiliary (n = 7), other (n = 3). SLM vs MLM:13/27; intact vs resected primary = 16/24. Median time from orig cancer dx to onset of MLM = 16 mos (range, 1 to 60 mos). No. of pulm mets at 1st appearance: 1 (n = 7); 2-5 (n = 17); 6-10 (n = 16). Median size of largest pulm met at 1st appearance = 6 mm (range, 0-39 mm); avg growth rate of largest pulm met = 0.18 mm/month (95% CI, 0.08-0.27). Avg growth rate of up to 5 largest lesions (sum) = 0.35 mm/month (95% CI, 0.07-0.64). Median f/u time prior to rx initiation for MLM = 172 days (range, 25-1547 days); 18 pts developed additional mets during their observation period. Rx modalities for LM: surg (n = 6), radiation (n = 18), systemic rx (n = 32). Addn details specific to cancer type, progression patterns, and pt outcomes will be presented at the meeting. Conclusions: The natural hx of LM varies across the spectrum of GI malignancies. Further larger-scale efforts to define patterns of growth of LM for different GI cancers, informed by size, #, and clinical/molecular features, are needed to guide appropriate timing and selection of rx as well as surveillance strategies.
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487
Background: Stereotactic body radiotherapy (SBRT) has been shown to be a safe and effective treatment for hepatobiliary cancers. However, little is known about the efficacy of ...adjuvant SBRT for resected liver tumors with positive margins. We examined the characteristics and outcomes of patients who received adjuvant SBRT for both primary and metastatic cancers of the liver. Methods: We retrospectively reviewed the charts of patients who had received liver SBRT from 2009-2015 at our institution. During that time frame, 11 patients were identified as having received adjuvant SBRT post resection. Patient data such as age, gender, portal vein thrombosis, cirrhosis, ECOG performance status, prior liver directed therapies, and SBRT dose were collected. Descriptive statistics were used for analysis given the small number of patients in this series. Results: Median age at the time of treatment was 63 years (range 51-79), and the majority of patients (72.7%) were male. Seven tumors (63.6%) were hepatocellular carcinomas, and 4 (36.4%) were adenocarcinomas. Of the tumors with adenocarcinoma histology, 3 were cholangiocarcinomas and one was metastatic colorectal cancer. Ten patients (90.9%) were treated for positive margins, and one was treated for inferior vena cava (IVC) invasion. Seven patients (63.6%) had no other liver-directed treatment prior to adjuvant SBRT. Two patients received systemic therapy prior to SBRT. Median EQD2 was 83.3 Gy (range 60-126), and 81.8% of patients received 5 fractions. There were no grade 3 or above late toxicities from treatment. Median follow-up was 14.1 months (range 5.4-38.1). None of the treated tumors progressed locally. Six patients (54.5%) progressed elsewhere in the liver, and one patient experienced distant metastatic progression. One patient experienced both intrahepatic progression and distant metastatic progression. Conclusions: Adjuvant SBRT appears to be a safe and feasible adjuvant treatment in patients with primary liver resection for either primary liver cancer or metastatic disease who are at high risk of recurrence.
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3572
Background: Anal cancer is an uncommon malignancy with numerous factors that influence treatment outcomes. Historically, HIV+ patients were restricted from entering clinical ...trials, limiting data on their outcomes to small retrospective reports. This study seeks to understand the factors related to anal cancer outcomes, specifically the differences between HIV+ and HIV- patients. Methods: Inclusion criteria was non-metastatic anal squamous cell carcinoma treated with a definitive course of chemotherapy and radiation between 2005 and 2018 at a single institution. Clinical data related to baseline characteristics, treatment parameters, and post-treatment follow-up were extracted for calculation of freedom from local recurrence (FFLR) and overall survival (OS). Univariate analysis (UVA) and multivariate analysis (MVA) were done using cox proportional hazard model, and FFLR and OS were calculated using the Kaplan-Meier method. Results: During the study period, 111 patient initiated definitive treatment for anal cancer. Median age was 56.7 years (IQR: 51.4-63.5), and 47% (N = 52) were HIV+. At median follow-up of 28 months, 12 and 24-month FFLR was 84.1% and 78.2% respectively, with 24-month OS of 87.3%. MVA demonstrated significant association between FFLR and T-stage HR 4.02 (95% CI: 2.14-7.55) p < 0.001, elapsed treatment time (median of 50 days) 1.08 (95% CI: 1.04-1.12) p < 0.001, and diagnosis to treatment start (median time of 15 weeks) 1.05 (95% CI: 1.01-1.08) p = 0.005. Additional analysis with log-rank test for FFLR demonstrated significant difference between patients taking < 50 days to complete treatment (p = 0.03), and < 15 weeks from diagnosis to treatment completion (p = 0.006). In HIV+ patients, post-treatment CD4 < 150 was significantly associated with worse OS on log-rank test (p = 0.016), with pretreatment CD4 values being non-significant. Conclusions: This study represents the largest single institution report of HIV positive patients treated for anal cancer. No difference in local recurrence or overall survival between HIV+ and HIV- patients was elucidated; however, HIV+ patients with lower post-treatment CD4 counts had worse OS. The most significant predictors of local recurrence were advanced T-stage, increased time from diagnosis to treatment initiation, and prolonged treatment time.
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