Change In Systemic Treatment Research Articles

Abscopal effect in metastatic breast cancer treated with stereotactic body radiotherapy in the absence of immunotherapy.

In this study, we aimed to assess the abscopal effect (AE) after CyberKnife stereotactic body radiotherapy (SBRT) in metastatic breast cancer patients without immunotherapy. We reviewed breast cancer patients who received SBRT with a fraction size of ≥ 6 Gy for metastatic lesions between July 2008 and December 2021. We selected patients who had at least one measurable extracranial lesion in addition to SBRT target lesions and were not treated with immunotherapy. A total of 40 SBRT cases from 34 patients were included in the analysis. The AE was defined as occurring before the overall progression of the disease, regardless of the use of systemic treatment. The median follow-up duration was 16.4 months. Among 40 SBRT cases, the AE was observed in 10 (25.0%) with a median interval of 2.1 months. Of these lesions, 70.0% did not progress for one year. In multivariate logistic regression analysis, no change in systemic treatment after SBRT was significantly associated with an increase in the AE (odds ratio [OR] = 1.428, 95% confidence interval [CI] = 1.108 - 1.841, p = 0.009). A post-SBRT neutrophil-to-lymphocyte ratio (NLR) of < 2 marginally increased the AE (OR = 1.275, 95% CI = 0.998 - 1.629, p = 0.060). However, a high SBRT dose and large planning target volume did not (p = 0.858 and 0.152, respectively) in univariate analysis. One out of four patients experienced the AE after SBRT in the absence of immunotherapy. The AE could occur more frequently when systemic treatment remains unchanged, and patients have a low NLR after SBRT.

Should organs at risk (OARs) be prioritized over target volume coverage in stereotactic ablative radiotherapy (SABR) for oligometastases? a secondary analysis of the population-based phase II SABR-5 trial

Background and PurposeStereotactic ablative radiotherapy (SABR) for oligometastases may improve survival, however concerns about safety remain. To mitigate risk of toxicity, target coverage was sacrificed to prioritize organs-at-risk (OARs) during SABR planning in the population-based SABR-5 trial. This study evaluated the effect of this practice on dosimetry, local recurrence (LR), and progression-free survival (PFS). MethodsThis single-arm phase II trial included patients with up to 5 oligometastases between November 2016 and July 2020. Theprotocol-specified planning objective was to cover 95 % of the planning target volume (PTV) with 100 % of the prescribed dose, however PTV coverage was reduced as needed to meet OAR constraints. This trade-off was measured using the coverage compromise index (CCI), computed as minimum dose received by the hottest 99 % of the PTV (D99) divided by the prescription dose. Under-coverage was defined as CCI < 0.90. The potential association between CCI and outcomes was evaluated. Results549 lesions from 381 patients were assessed. Mean CCI was 0.88 (95 % confidence interval [CI], 0.86–0.89), and 196 (36 %) lesions were under-covered. The highest mean CCI (0.95; 95 %CI, 0.93–0.97) was in non-spine bone lesions (n = 116), while the lowest mean CCI (0.71; 95 % CI, 0.69–0.73) was in spine lesions (n = 104). On multivariable analysis, under-coverage did not predict for worse LR (HR 0.48, p = 0.37) or PFS (HR 1.24, p = 0.38). Largest lesion diameter, colorectal and ‘other’ (non-prostate, breast, or lung) primary predicted for worse LR. Largest lesion diameter, synchronous tumor treatment, short disease free interval, state of oligoprogression, initiation or change in systemic treatment, and a high PTV Dmax were significantly associated with PFS. ConclusionPTV under-coverage was not associated with worse LR or PFS in this large, population-based phase II trial. Combined with low toxicity rates, this study supports the practice of prioritizing OAR constraints during oligometastatic SABR planning.

Stereotactic Ablative Radiotherapy (SABR) for Oligometastatic Gynecologic Malignancies: A Single Institution Experience

<h3>Purpose/Objective(s)</h3> There is a paucity of data regarding use of SABR for gynecologic malignancies. This retrospective analysis was performed to evaluate the feasibility and efficacy of this treatment for this patient population. <h3>Materials/Methods</h3> 20 patients requiring 30 sites of treatment were treated at our institution. 10 patients had endometrial cancer (50%), 9 patients had ovarian cancer (45%) and 1 patient had cervical cancer (5%). 20 sites (67%) were treated with volumetric modulated arc therapy and 10 sites (33%) were treated with dynamic three-dimensional arc therapy. Sites treated included pelvic or abdominal lymph nodes (67%), neck or axillary nodes (13%), bone (10%), lung (7%), and mediastinal nodes (3%). Dose delivered was 30 Gy in 5 fractions (57%), 24-27 Gy in 3 fractions (33%), or 45-50 Gy in 5 fractions (10%). <h3>Results</h3> Median follow-up was 19 months. Grade 3-4 toxicity was not observed in any patients. Progression was defined as requiring a systemic treatment change or requiring another course of SABR. At the time of last follow-up, 10 patients (50%) had progressed. 6 patients (30%) required a change in systemic treatment. True in-field recurrence was not observed in any patients. Median progression free survival was 9.5 months. Median overall survival was not reached. 5 patients (25%) required no systemic therapy of any kind to maintain disease-free status. <h3>Conclusion</h3> SABR was well tolerated and associated with excellent local control. The use of SABR allowed many patients to delay change in systemic treatment, or to avoid systemic treatment altogether. The median progression free survival of 9.5 months in this cohort compares favorably to that expected with second- or third-line systemic therapy (4.1 and 1.7 months, respectively, for ovarian cancer). SABR should be strongly considered for patients with oligometastatic gynecologic malignancies.

Progression-Free Survival and Local Control After SABR for up to 5 Oligometastases: An Analysis From the Population-Based Phase 2 SABR-5 Trial

Despite increasing utilization of SABR for oligometastatic cancer, prospective outcomes are lacking. The purpose of this study was to determine progression-free survival (PFS), local control (LC), and prognostic factors from the population-based phase 2 SABR-5 trial. The SABR-5 trial was a single-arm phase 2 study with the primary endpoint of toxicity, conducted at the 6 regional cancer centers across British Columbia (BC), Canada, during which time SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced oligometastatic disease) underwent SABR to all lesions. Patients were 18 years of age or older, had an Eastern Cooperative Oncology Group score of 0 to 2, and had life expectancy ≥ 6 months. The secondary outcomes of PFS and LC are presented here. Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). Median PFS was 15 months (95% confidence interval [CI], 12-18). LC at 1 and 3 years were 93% (95% CI, 91-95) and 87% (95% CI, 84-90), respectively. On multivariable analysis, increasing tumor diameter (hazard ratio [HR], 1.09; P < .001), declining performance status (HR, 2.13; P < .001), disease-free interval <18 months (HR, 1.52; P=.003), 4 or more metastases at SABR (HR, 1.48; P=.048), initiation or change in systemic treatment (HR, 0.50; P < .001), and oligoprogression (HR, 1.56; P=.008) were significant independent predictors of PFS. Tumor diameter (sub-hazard ratio [SHR], 1.28; P < .001), colorectal histology (SHR, 4.33; P=.002), and "other" histology (SHR, 3.90; P < .001) were associated with worse LC. In this population-based cohort including patients with genuine oligometastatic, oligoprogressive, and induced oligometastatic disease, the median PFS was 15 months and LC at 3 years was 87%. This supports ongoing efforts to randomize patients in phase 3 trials, even outside the original 1 to 5 metachronous oligometastatic paradigm.

Intravitreal fluocinolone acetonide 0.19 mg (Iluvien®) for the treatment of uveitic macular edema: 2-year follow-up of 20 patients

To evaluate intravitreal 0.19mg fluocinolone acetonide implant (FAi) (Iluvien®) for the treatment of chronic non-infectious uveitis with associated cystoid macular edema (CME). A retrospective review of medical reports from a single Danish tertiary centre including 20 patients (20 eyes), treated with 0.19mg FAi for non-infectious uveitic CME. The primary endpoints were change in best corrected visual acuity (BCVA) and central retinal thickness (CRT). The secondary endpoints were recurrence rate, change in systemic treatment, and intraocular pressure (IOP). Mean follow-up of the 20 eyes was 2.3 ± 1.1years. BCVA improved at 6 (p = 0.13), 12 (p = 0.05), 18 (p = 0.03), and 24months and CRT decreased at 6 (p = 0.004), 12 (p = 0.006), 18, and 24months after 0.19mg FAi. Within 18months after implantation, four of 14 patients (28.6%) relapsed. Three of five patients discontinued systemic corticosteroids within 4months and one patient continued with reduced dose. Five of 10 patients receiving disease-modifying antirheumatic drugs (DMARDs) at time of implantation discontinued within 1year. No patients started new systemic treatment. Eight eyes were treated with topical IOP-lowering medication at the time of implantation, of these two later underwent trabeculectomy. There were no complications associated with previous glaucoma surgery. This long-term follow-up study showed that intravitreal treatment with 0.19mg FAi should be considered in the treatment of chronic non-infectious uveitic CME in selected patients. This treatment is safe even in selected glaucoma patients and may offer reduction or cessation of local or systemic anti-inflammatory treatment.

Abstract PS14-20: Retrospective analysis of time to progression intracranially in HER2+ breast cancerpatients with brain metastases who receive treatment with radiation

Abstract Human epidermal growth factor receptor 2 (HER2) positive (+) breast cancer is a disease with distinct clinicopathological features. Survival for women with HER2+ disease has increased with the development of novel systemic therapeutic agents, however the brain is increasingly reported as the first site of relapse. As patients with HER2-positive breast cancer live longer, CNS progression after radiation therapy and / or surgery is an emerging clinical challenge. The average progression free interval intracranially is unknown for women who receive radiation for brain metastases while on modern HER2 targeted therapy. Multiple novel systemic agents are under investigation for the treatment of HER2 positive breast cancer metastatic to the brain. In order to establish a historical control for early phase clinical trials, understanding this time to progression is critical. In our retrospective chart review, we sought to determine the time to progression intracranially for women with HER2+ breast cancer who receive CNS radiation and/or surgery while on modern HER2 targeted systemic therapy. We present preliminary results from our review of 48 patients with HER2+ breast cancer with brain metastases treated at two academic referral centers between 2010-2017. 36 of these patients received some form of local therapy for brain metastases. Mean age at the time of diagnosis with primary breast cancer was 52, with a mean age of 55 at the time of diagnosis of brain metastases. The minority of patients (n=16) were stage IV at the time of their initial diagnosis. Standard of care systemic treatment was given in 43/48 cases. Mean length of time from the diagnosis of the primary breast cancer to the diagnosis of brain metastases was 34.6 months, including 3 patients diagnosed at initial presentation and at the other extreme, 2 patients diagnosed 9 years after their primary diagnosis of cancer. Of the patients who received treatment for brain metastases and for whom data was available (n=33), mean time from first treatment for brain metastases to first brain recurrence was 8.24 months (range: 1 to 24 months). 7 patients (21%) recurred within 3 months. In 9 patients mortality data was available. Mean time from treatment to death was 20 months (range 1 - 58 months). For patients who underwent surgery alone as primary treatment, mean time until first recurrence was 7.1 months (n=14), compared with a mean of 7.8 months for patients who received WBRT (n=26). Patients who received both surgery and radiation as a primary treatment had a mean time from first treatment to recurrence of 11.5 months (n=4). Only 34% of patients changed systemic treatment after the diagnosis of brain metastases. 5 patients had brain metastases as their only site of measurable disease. Only 1 of these patients had a change in systemic treatment after the diagnosis of brain metastases. These results suggest that the time from initial local treatment for brain metastases to recurrence is devastatingly short. Future clinical trials in metastatic HER2+ breast cancer should consider the impact novel therapeutics have on brain metastases in addition to overall and progression free survival. These data provide a historical reference for evaluating the impact of novel therapies on HER2-postive brain metastases. Citation Format: Jacklyn Marie Nemunaitis, Krisha Mehta, Selina Liu, Ursa Brown-Glaberman, Alison Stopeck. Retrospective analysis of time to progression intracranially in HER2+ breast cancerpatients with brain metastases who receive treatment with radiation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-20.

Metastasis-directed Therapy Prolongs Efficacy of Systemic Therapy and Improves Clinical Outcomes in Oligoprogressive Castration-resistant Prostate Cancer

BackgroundAvailable therapies for castrate-resistant prostate cancer (CRPC) confer minimal survival advantage; thus, there is interest in metastasis-directed therapy (MDT) for oligometastatic or oligoprogressive disease to improve outcomes. Here, we describe outcomes of oligoprogressive CRPC treated with stereotactic ablative radiotherapy (SABR). ObjectiveTo report outcomes of oligoprogressive CRPC treated with MDT using SABR. Design, setting, and participantsPatients with oligoprogressive CRPC were retrospectively evaluated, and outcomes following MDT were reported. Outcomes were additionally compared with oligoprogressive CRPC treated with change in systemic therapy alone. InterventionSABR to oligoprogressive lesions. Outcome measurements and statistical analysisOutcomes of interest were time to prostate-specific antigen (PSA) failure, time to next intervention (TTNI), distant metastasis-free survival (DMFS), and overall survival. Survival analysis was performed using the Kaplan-Meier method, and univariable analysis and multivariable analysis (MVA) were performed. Results and limitationsA total of 68 patients were included. After MDT, median time to PSA recurrence, TTNI, and DMFS were 9.7, 15.6, and 10.8 months, respectively. A total of 112 lesions were treated, and the cumulative incidences of local failure at 12 and 24 months were 2.1% and 13.8%, respectively. Factors associated with the risk of local recurrence on univariable analysis were age (hazard ratio [HR] 1.07, p = 0.03) and Gleason grade group (HR 2.20, p = 0.07). Compared with change in systemic therapy alone (n = 52), MDT (n = 31) was associated with improved median time to PSA failure (9.7 vs 4.2 months, p = 0.066)), TTNI (14.9 vs 8.8 months, p = 0.025), and DMFS (12.7 vs 8.9 months, p = 0.045), and remained associated with improved outcomes on MVA. ConclusionsIn a retrospective cohort of oligoprogressive CRPC patients, MDT was associated with favorable outcomes and improved cancer control as compared with change in systemic treatment alone. Future prospective trials are needed to confirm these findings. Patient summaryIn this report, we retrospectively analyzed outcomes of patients with oligoprogressive castrate-resistant prostate cancer treated with radiation therapy to progressing lesions. Our results suggest that treatment of these lesions with radiation therapy can result in sustained periods of disease-free survival and might add benefit in addition to systemic therapy at the time of progression. These results need to be verified in a prospective trial to identify the optimal integration of radiation therapy into metastatic castrate-resistant prostate cancer.

Abstract P2-20-07: Assessment of leptomeningeal carcinomatosis management and outcomes in patients with advanced breast cancer from 2005 to 2015: A single institution experience

Abstract Background Leptomeningeal carcinomatosis (LMC) is a complication of advanced malignancies wherein metastatic disease invades the meninges of the central nervous system via contiguous spread from bone or brain metastases or hematogenous spread from systemic disease. Breast cancer is the most common solid tumor etiology of LMC. Approximately 5% of patients (pts) with breast cancer develop LMC. LMC has a median survival of 4 weeks when untreated and 8-16 weeks with treatment. The diagnosis of LMC remains challenging with only 60% of pts having cerebrospinal fluid (CSF) positive for malignant cells. There is no generally accepted standard of care for treatment of LMC but it may involve intrathecal or systemic chemotherapy, whole brain or spinal radiotherapy, or a combination of modalities. We aimed to assess detection and treatment strategies of LMC in pts with breast cancer treated at the Ohio State University Comprehensive Cancer Center-James (OSUCCC-James) to better characterize the disease and guide clinical care. Methods An IRB-approved single-institution retrospective protocol was developed. Medical records of 469 pts who had undergone a procedure related to LMC diagnosis or treatment were identified and reviewed to determine study eligibility. Comprehensive data was obtained through information warehouse and chart review was performed for the eligible 69 pts with breast cancer diagnosed with LMC and treated at the OSUCCC-James between January 1, 2005 and December 31, 2015. Descriptive statistics were used to summarize demographic and clinical characteristics. Overall survival (OS) was defined as time from LMC diagnosis to death or last known follow-up, and was generated using Kaplan Meier methods. Comparisons in OS between groups were analyzed using Log-rank tests. Results Sixty-nine female pts were included in the analysis with the following characteristics: median age 55.7 years (range: 48-60.6 years), Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (86%; N=59), and Caucasian (78%; N=54). They had the following subtypes hormone receptor positive (HR +), and human epidermal growth factor receptor (HER2) negative (61%, N=42), triple negative (25%, N=17) and HER2 positive (10%, N=7). The most common sites of metastases included bone (42%), brain (28%), and lung (12%). The median time between the diagnosis of first metastasis and LMC was 0.9 years (range: 0-3.2 years). Of the 40 (58%) pts who underwent lumbar puncture, 21 (52%) pts had positive CSF cytology. Sixty-eight pts (99%) had MRI findings suggestive of LMC. The most common treatment modalities were systemic chemotherapy (N=14, 41%), radiotherapy (N=12, 35%), and intrathecal chemotherapy (N=14, 35%). Fifty-six pts (81%) had a change in systemic chemotherapy agent after diagnosis. The median OS of all pts was 2.4 months (95% confidence interval: 1.2-4.4). Pts with ER+/PR+/HER2- had a better OS (4.4 months, 95%CI 1.5, 6.1)) compared to those with HER2+ (1.3 months, 95%CI 0.2, 1.9) or ER-/PR-/HER2- (0.6 months, 95%CI 0.0, 15.8) subtypes (p-value=0.004). Pts with negative CSF cytology had a greater OS compared to those with positive CSF cytology (9.8 vs. 0.7 months, p=0.026) and pts who had a change in systemic treatment had a greater OS compared with patients who had no new treatment (2.5 months vs. 1.2 months, p =0.039). No significant difference was seen in OS between ECOG performance status groups. Conclusions LMC is a relatively rare yet devastating complication of breast cancer. Based on our institutional experience, LMC remains a clinical challenge and is associated with poor OS. Pts with triple negative and HER2 positive disease and those with high disease burden fare worse. Pts who had change in systemic therapy fare better. Dedicated clinical trials are urgently needed to improve outcomes. Citation Format: Hannah Rinehardt, Nicole Williams, Evan Morgan, Mahmooud Kassem, Marilly Palettas, Abdul Miah, Iyad Alnahhas, Pilar Guillermo Prieto Eibl, Anupama Suresh, Vinay Puduvalli, Pierre Giglio, Maryam Lustberg, Robert Wesolowski, Sagar Sardesai, Daniel Stover, Jeffrey VanDeusen, Jose Bazan, Bhuvaneswari Ramswamy, Anne Noonan. Assessment of leptomeningeal carcinomatosis management and outcomes in patients with advanced breast cancer from 2005 to 2015: A single institution experience [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-20-07.

Targeted Therapy With or Without Dose-intensified Radiotherapy in Oligoprogressive Disease in Oncogene Addicted Lung Tumours

Background: Optimal management of advanced NSCLC patients with actionable mutations, developing limited oligoprogressive disease (OPD) on TKI treatment is uncertain with subsequent systemic therapy options limited in the UK. The additional benefit with SBRT to ablate OPD sites prior to change in systemic treatment is an important question. This study is designed to assess whether SBRT treatment to OPD sites can increase the time patients derive benefit from TKI therapy prior to further disease progression.

Extramedullary Hematopoiesis of the Conjunctiva Presenting as Active Systemic Disease in a Patient With Myelofibrosis

To report the clinicopathological correlation of extramedullary hematopoiesis (EMH) of the conjunctiva in a patient with a history of myelofibrosis. Case report. Elevated pink conjunctival lesions developed bilaterally in a 73-year-old man who had been treated for myelofibrosis for 13 years. EMH was detected in the examination of tissue from the lesion of the inferior fornix of the right eye. The appearance of conjunctival lesions in a patient with myelofibrosis may indicate underlying pathology of EMH that may necessitate a change in systemic treatment of this condition.

Interdisciplinary counseling service for renal malignancies: A patient-centered approach to raise guideline adherence

ObjectivesTumor boards have become an integral part of high-quality cancer care, but in general, patients are not directly involved. To overcome this weakness, we established an interdisciplinary counseling service for renal malignancies where 4 specialists talked to the patient at once. We evaluated this approach from the patients’ and physicians’ perspective. Materials and methodsFor 3 months, we assessed organizational and clinical data. Within a standardized telephone interview lasting for 14±8 minutes, we explored the patients’ view 1 week after counseling. A focus group contributed the physicians’ perspective. Costs and revenues were calculated from the hospital’s perspective. ResultsWe included 52 consecutive patients aged 62±10 years. Patients’ initiative for a “second opinion” triggered 37% of all appointments. Patients had localized (52%) and systemic (48%) disease presenting with primary diagnosis (48%), relapse (27%), or under continuous therapy (25%). The treatment strategy was changed significantly in 16 of 30 (53%) patients reporting a specific external opinion. The most frequent changes in recommendation were nephron-sparing surgery instead of radical nephrectomy in 8 cases and divergent judgments on restaging causing changes in systemic treatment in 6 cases. We successfully interviewed 43 of 52 patients. Overall, patients rated the consultation as very positive and only 1 patient (2%) was dissatisfied. Patients rated the quality of interpersonal interaction as very positive and said they would recommend the consultation service to others. Disease state was not associated with ratings. Physicians expressed a very positive opinion, highlighting the patients’ benefit and very constructive case discussions. Nevertheless, they report remarkable efforts concerning time investment and effective coordination of medical experts. We estimated a deficit of 39 Euro per patient given the German health care system. There might be relevant secondary positive economic effects for the hospital such as recommendations from one patient to another leading to acquisition of additional patients. ConclusionsPatient involvement in multidisciplinary tumor boards is feasible and well regarded by patients and physicians likewise. By stimulating interdisciplinary collaboration, the interdisciplinary counseling service improves patient satisfaction and clinical decision making. The interdisciplinary counseling service corrected half of the external treatment plans for better guideline adherence. These positive effects come at the price of higher resource utilization. (www.germanctr.de, number DRKS00003279).

Have Changes in Systemic Treatment Improved Survival in Patients with Breast Cancer Metastatic to the Brain?

Newly developed systemic treatment regimens might lead to improved survival also in the subgroup of breast cancer patients that harbour brain metastases. In order to examine this hypothesis, a matched pairs analysis was performed that involved one group of patients, which were treated after these new drugs were introduced, and one group of patients, which were treated approximately 10 years earlier. The two groups were well balanced for the known prognostic factors age, KPS, extracranial disease status, and recursive partitioning analysis class, as well as for the extent of brain treatment. The results show that the use of systemic chemotherapy has increased over time, both before and after the diagnosis of brain metastases. However, such treatment was performed nearly exclusively in those patients with brain metastases that belonged to the prognostically more favourable groups. Survival after whole-brain radiotherapy has remained unchanged in patients without further active treatment. It has improved in prognostically better patients and especially patients that received active treatment, where the 1-year survival rates have almost doubled. As these patient groups were small, confirmation of the results in other series should be attempted. Nevertheless, the present results are compatible with the hypothesis that improved systemic therapy might contribute to prolonged survival in patients with brain metastases from breast cancer.