Locoregional Progression Research Articles

GPP04 Presentation Time: 8:30 AM: What is Appropriate Target Delineation for MRI-Based Brachytherapy for Medically Inoperable Endometrial Cancer?

<h3>Purpose</h3> While the incidence of medically inoperable endometrial cancer (MIEC) is anticipated to rise within the growing elderly population, practice patterns demonstrate persistent underutilization of brachytherapy (BT). Contemporary Image-guided BT (IGBT) offers superior target dose escalation while sparing adjacent organs at risk. However, the volumetric target of IGBT techniques is not well established. We propose a high-risk CTV (HRCTV) concept and report associated rates of local control and toxicity. <h3>Materials and Methods</h3> A retrospective review identified all patients with MIEC receiving definitive external beam radiotherapy (EBRT) followed by MRI-based IGBT at a single institution. BT dose was prescribed to a HRCTV defined as gross tumor volume plus endometrial cavity with a planning goal of a summed equivalent dose at 2Gy/fraction (EQD2) D90 of 85Gy or greater. An additional intermediate-risk volume (IRCTV) was developed by global 5mm expansion upon this HRCTV, removing any volume entering into organs at risk (OAR). The myometrium and uninvolved uterine body was not defined as target volume. OARs including rectum, bladder, sigmoid and bowel were limited to EQD2 constraints directly adapted from cervical cancer. Late gastrointestinal (GI), genitourinary (GU), and vaginal toxicity events were graded using CTCAE, version 5.0. Clinical endpoints including local progression-free survival (LPFS), progression-free survival (PFS), and overall survival (OS) were estimated via the Kaplan Meier method. <h3>Results</h3> 32 patients received MRI-based HDR-BT for MIEC between 12/2015 and 8/2020, with a median follow up of 19.8 months (IQR 8.9 - 27.6 months). Patients were a median 71.5 years at diagnosis (range, 43 - 91 years), with a median ECOG 1 performance status (IQR 1 - 2). FIGO stages included 1A (56%), IB (16%), II (3%), III (22%), and IV (3%). Common histologies included endometrioid (56%), serous adenocarcinoma (22%), and carcinosarcoma (13%). All patients completed EBRT (45 Gy/25 fractions, 69%; 50.4 Gy/28 fractions, 16%; other, 16%) followed by MRI-guided HDR-BT (27.5 Gy/5 fractions, 66%; 28 Gy/4 fractions, 28%; other, 6%). Composite dosimetry included the following median EQD2 values: D90 HRCTV 91.3 Gy (IQR 88.2 - 96.4 Gy), D98 HRCTV 78.2 Gy (73.7 - 82.6 Gy), D90 IRCTV 73.4 Gy (69.9 - 76.0 Gy), D2cc Bladder 72.9 Gy (66.7 - 76.4 Gy), D2cc Rectum 57.0 Gy (52.1 - 66.0 Gy), D2cc Sigmoid 65.0 Gy (63.3 - 70.3 Gy), D2cc Bowel 60.2 Gy (53.2 - 66.0 Gy), and D2cc Vagina 82.9 Gy (79.9 - 90.6 Gy). 16% of patients received hormonal therapy, and 3% of patients received chemotherapy. Figure 1 provides LPFS, PFS, and OS. There were 14 (44%) total deaths, 3 local recurrences (9%), 3 nodal recurrences (9%), and 5 distant recurrences (16%). 2-year LPFS was 88.8%, and 2-year OS was 65.8%, with no locoregional or distant progression observed beyond 24 months post-BT. For the 3 patients with local progression, median D90 HRCTV was 99.2 Gy (range 77.9 - 103.5 Gy), D98 HRCTV 80.2 Gy (68.6 - 89.4 Gy), and D90 IRCTV 73.3 Gy (66.0 - 83.5 Gy). For patients with stage I/II disease (n=24), LPFS was 100% at 12 months and 94% (95% CI 81.9 - 100%) at 24 months. 23 (72%) patients experienced no RT-related toxicity. Two grade 3+ toxicities (6%) were observed: one grade 3 vomiting event prompting hospitalization and one grade 5 GI bleed presumed secondary to RT-induced proctitis in the setting of longstanding clopidogrel use. <h3>Conclusions</h3> Patients with MIEC receiving definitive EBRT followed by MRI-based IGBT demonstrated high rates of long-term local control with a favorable toxicity profile, when dose was prescribed to the MRI-defined GTV and endometrial cavity. These data compare favorably to historical controls despite a significant proportion of patients with locally advanced disease and/or aggressive histology.

Evaluation of Practice Patterns and Outcomes after Implementing SMART for Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> Stereotactic MRI-guided adaptive radiation therapy (SMART) enables safe dose escalation for locally advanced, borderline resectable, and medically inoperable pancreatic cancer and has shown favorable toxicity and survival outcomes. In late 2018, our institution commissioned SMART for these patients, making it available to all patient referrals. We wanted to review changes in our patient population and differences in clinical outcomes for patients before and after the implementation of SMART. <h3>Materials/Methods</h3> In this IRB approved analysis, we retrospectively reviewed 167 consecutive patients from 2015-2021 with locally advanced, borderline resectable, or medically unresectable pancreatic cancer who were treated with radiation therapy. Chemoradiation (chemoRT) was defined as any 28-30 fraction radiation regimen that included concurrent chemotherapy. SMART was defined as 50 Gy over 5 consecutive daily fractions without concurrent chemotherapy. Baseline patient characteristics were compared between groups. Overall survival (OS) was evaluated by Kaplan-Meier (KM) and log-rank test. Univariate (UVA) and multivariate analysis (MVA) were also performed on multiple treatment variables. <h3>Results</h3> Of the patients included, 58 received chemoRT (2015-2018) and 109 received SMART (2018-2021). Median follow up from time of diagnosis for the chemoRT and SMART cohorts were 53.7 months and 29.2 months respectively. Cohorts did not have significant differences in age, gender, race, T or N staging, rates of surgery or surgical margin status. Patients receiving SMART had overall worse performance (p = 0.011) including a lower percentage of PS 0 patients (22.9% vs 44.8%) and a higher percentage of PS 2+ patients (34% vs 15.5%). Similarly, the SMART patients did numerically more often have locally advanced (50% vs 43%) and medically inoperable (26% vs 21%) disease (p = 0.294). The SMART cohort did have longer neoadjuvant chemotherapy with mean of 3.5 months vs 2.3 months in the chemoRT cohort (p = 0.002). There was no OS difference between each group when measured from diagnosis (p=0.79) or from first day of radiation (p=0.2). Median survival in the chemoRT and SMART groups was 18.7 vs 17.4 months from diagnosis. When including only PS 0-1 patients, the median survival in the chemoRT and SMART groups was 18.8 vs 22.3 months (p=0.37). There was also no difference in locoregional control, distant control, or progression free survival using KM. On MVA positive prognostic factors for OS from diagnosis included ECOG <2 (HR 0.54, p=0.015), increasing months of neoadjuvant chemo (HR 0.88, p=0.004) and pancreatectomy (HR 0.14, p <0.001). <h3>Conclusion</h3> Despite the fact that the patient cohort receiving radiation therapy per the SMART approach had poorer performance status compared with chemoRT, OS was not significantly different. The multidisciplinary team was highly supportive of SMART with increased patients being treated.

Patterns of Locoregional Relapse after Radiotherapy for High-Risk Neuroblastoma: A Multi-Institutional Study

<h3>Purpose/Objective(s)</h3> In high-risk neuroblastoma (HRNBL), locoregional relapse (LRR) is a significant contributor to treatment failure despite intensive multimodal therapy, including radiotherapy (RT). A recent Children's Oncology Group study found no benefit to boost RT for gross residual disease. Thus, we sought to characterize patterns of LRR after RT for patients (pts) with HRNBL. <h3>Materials/Methods</h3> The Institutional Review Boards approved this multi-institutional retrospective cohort study of pts who received ≥1 autologous stem cell transplant (ASCT) and external beam RT for HRNBL from 1997-2021. Pts who progressed prior to ASCT were excluded. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. In-field and marginal recurrences were defined as sites receiving >12 Gy and ≤12 Gy, respectively. Follow-up (FU) was from end of RT. Event-free survival (EFS) and overall survival (OS) were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse, secondary cancer, and death with Gray's test. <h3>Results</h3> We identified 311 pts with median age at diagnosis of 3.0 years (range: 0.02-28.7). The most common primary site was adrenal/abdominal (n=280, 90.0%). 271 (87.1%), 126 (40.5%) and 240 (77.2%) pts had metastatic disease at diagnosis, <i>MYCN</i> amplification, and unfavorable histology, respectively. 108 pts (34.7%) received proton RT. Of the 167 (53.7%) pts who underwent tandem ASCT, 68 (40.7%) received TBI-based conditioning. No pts received TBI after 2012. Of the 115 (37.0%) pts with subtotal resection (STR), 54 (47.0%) received ≥36 Gy. 202 (65.0%) received post-Consolidation anti-GD2 immunotherapy. Median FU was 6.5 years (range: 0.01-22.4). For the cohort, 5-year CILP, EFS and OS were 10.8%, 66.7% and 78.9%, respectively. After STR, ≥36 Gy did not decrease 5-year CILP (11.8% vs. 13.1%, p=0.80). 5-year CILP was significantly lower for pts receiving immunotherapy (6.4% vs. 21.5%, p<0.001). For pts receiving immunotherapy, 5-year CILP was similar for photon and proton RT (6.1% vs. 6.6%, p=0.78). Of the 29 pts with LRR and imaging for review, 13 (44.8%) were in-field only, 6 (20.7%) were marginal only, and 10 (34.5%) were both in-field and marginal. In pts receiving immunotherapy, 4 LRRs were in-field only, 3 were marginal only, and 4 were both in-field and marginal with 6/7 (85.7%) marginal recurrences occurring at sites of disease present at diagnosis with complete response after induction chemotherapy. <h3>Conclusion</h3> LRR contributes to treatment failure in HRNBL with most occurring in-field. CILP was lower for pts receiving immunotherapy and there was no difference in CILP between photon and proton RT. In pts receiving immunotherapy, approximately 25% of LRRs were marginal only. Future studies are needed to examine the optimal RT fields and dose in the era of anti-GD2 immunotherapy.

Dose-escalated re-irradiation improves outcome in locally recurrent head and neck cancer – Results of a large multicenter analysis

To determine efficacy and prognostic parameters of definitive re-irradiation of locoregionally recurrent squamous cell carcinoma of the head and neck (HNSCC). Materials and methodsPatients with locoregionally recurrent or second primary HNSCC undergoing re-irradiation with modern radiotherapy technique were eligible for this multicentric retrospective analysis. Main endpoints were overall survival (OS), progression-free survival (PFS) and locoregional control (LC). Univariate analyses were performed using the Kaplan Meier Method (log-rank). For multivariable analysis, Cox regression was used. ResultsA total of 253 patients treated between 2009 and 2020 at 16 university hospitals in Germany were included. The median follow up was 27.4 months (range 0.5–130). The median OS and PFS were 13.2 (CI: 10.7 – 15.7) months and 7.9 (CI: 6.7 – 9.1) months, respectively, corresponding to two-year OS and PFS rates of 29 % and 19 %. Rates of locoregional progression and “in-field-failure” were 62 % and 51 % after two years. Multivariable Cox regression analysis identified good ECOG performance status and high radiation dose as independent prognostic parameters for OS. Doses above 50 Gy (EQD2) achieved longer median OS of 17.8 months (vs 11.7 months, p < 0.01) and longer PFS of 9.6 months (vs 6.8 months, p < 0.01). In addition, there was a trend for worse survival in patients with tracheostomy (multivariable, p = 0.061). Concomitant systemic therapy did not significantly impact PFS or OS. ConclusionRe-irradiation of locally recurrent or second primary HNSCC is efficient, especially if doses above 50 Gy (EQD2) are delivered. ECOG performance score was the strongest prognostic parameter for OS and PFS.

Causes of Death Among Patients With Initially Inoperable Pancreas Cancer After Induction Chemotherapy and Ablative 5-fraction Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy

PurposeNearly all patients with pancreatic ductal adenocarcinoma (PDAC) eventually die of progressive cancer after exhausting treatment options. Although distant metastases (DMs) are a common cause of death, autopsy studies have shown that locoregional progression may be directly responsible for up to one-third of PDAC-related deaths. Ablative stereotactic magnetic resonance-guided adaptive radiation therapy (A-SMART) is a novel treatment strategy that appears to improve locoregional control compared with nonablative radiation therapy, potentially leading to improved overall survival. Methods and MaterialsA single-institution retrospective analysis was performed of patients with nonmetastatic inoperable PDAC treated between 2018 to 2020 using the MRIdian Linac with induction chemotherapy, followed by 5-fraction A-SMART. We identified causes of death that occurred after A-SMART. ResultsA total of 62 patients were evaluated, of whom 42 (67.7%) had died. The median follow-up time was 18.6 months from diagnosis and 11.0 months from A-SMART. Patients had locally advanced (72.6%), borderline resectable (22.6%), or resectable but medically inoperable PDAC (4.8%). All patients received induction chemotherapy, typically leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (69.4%) or gemcitabine/nab-paclitaxel (24.2%). The median prescribed dose was 50 Gy (range, 40-50), corresponding to a median biologically effective dose of 100 Gy10. Post-SMART therapy included surgery (22.6%), irreversible electroporation (9.7%), and/or chemotherapy (51.6%). Death was attributed to locoregional progression, DMs, cancer-related cachexia/malnutrition, surgery/irreversible electroporation complications, other reasons not due to cancer progression, or unknown causes in 7.1%, 45.2%, 11.9%, 9.5%, 11.9%, and 14.3% of patients, respectively. Intra-abdominal metastases of the liver and peritoneum were responsible for 84.2% of deaths from DMs. ConclusionsTo our knowledge, this is the first contemporary evaluation of causes of death in patients with PDAC receiving dose-escalated radiation therapy. We demonstrated that the predominant cause of PDAC-related death was from liver and peritoneal metastases; therefore novel treatment strategies are indicated to address occult micrometastatic disease at these sites.

1734MO Hypoxic bladder cancers have a poorer outcome following hypofractionated vs conventionally fractionated radiotherapy in the BC2001 and BCON randomised trials

Radical treatment for muscle-invasive bladder cancer (MIBC) involves radiotherapy with radiosensitiser or cystectomy currently selected subjectively (patient/clinician preference). The West 24-gene bladder cancer hypoxia signature predicted benefit from hypoxia-modifying radiosensitisation (carbogen+nicotinamide, CON) in BCON trial. The BC2001 trial showed combining chemotherapy (5-FU, mitomycin-C) with radiotherapy (RT) improves loco-regional progression free survival. Both BCON and BC2001 allowed conventional (62Gy/32 fractions) or hypofractionated (55Gy/20 fractions) RT.

Percutaneous local tumor ablation vs. stereotactic body radiotherapy for early-stage non-small cell lung cancer: a systematic review and meta-analysis.

Background:Percutaneous local tumor ablation (LTA) and stereotactic body radiotherapy (SBRT) have been regarded as viable treatments for early-stage lung cancer patients. The purpose of this study was to compare the efficacy and safety of LTA with SBRT for early-stage non-small cell lung cancer (NSCLC).Methods:PubMed, Embase, Cochrane library, Ovid, Google scholar, CNKI, and CBMdisc were searched to identify potential eligible studies comparing the efficacy and safety of LTA with SBRT for early-stage NSCLC published between January 1, 1991, and May 31, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were applied to estimate the effect size for overall survival (OS), progression-free survival (PFS), locoregional progression (LP), and adverse events.Results:Five studies with 22,231 patients were enrolled, including 1443 patients in the LTA group and 20,788 patients in the SBRT group. The results showed that SBRT was not superior to LTA for OS (HR = 1.03, 95% CI: 0.87–1.22, P = 0.71). Similar results were observed for PFS (HR = 1.09, 95% CI: 0.71–1.67, P = 0.71) and LP (HR = 0.66, 95% CI: 0.25–1.77, P = 0.70). Subgroup analysis showed that the pooled HR for OS favored SBRT in patients with tumors sized >2 cm (HR = 1.32, 95% CI: 1.14–1.53, P = 0.0003), whereas there was no significant difference in patients with tumors sized ≤2 cm (HR = 0.93, 95% CI: 0.64–1.35, P = 0.70). Moreover, no significant differences were observed for the incidence of severe adverse events (≥grade 3) (OR = 1.95, 95% CI: 0.63–6.07, P = 0.25) between the LTA group and SBRT group.Conclusions:Compared with SBRT, LTA appears to have similar OS, PFS, and LP. However, for tumors >2 cm, SBRT is superior to LTA in OS. Prospective randomized controlled trials are required to determine such findings.INPLASY Registration Number:INPLASY202160099

Effect of treatment interruptions and outcomes in cancer patients undergoing radiotherapy during the first wave of COVID-19 pandemic in a tertiary care institute

IntroductionCOVID-19 patients with cancer had poorer outcomes due to immunosuppression during cancer care, poor general condition, and other comorbidities. The study was conducted to present the real-world analysis of the effect of treatment interruptions on the outcomes of patients treated with radiation therapy during the first wave of the COVID-19 pandemic in a tertiary care institute in India.Materials and methodsThe study is a retrospective observational cohort study on cancer patients undergoing radiation therapy from March 2020 to January 2021. The study’s primary outcome was to analyze the effect of treatment interruptions on the outcomes of patients treated with radiation therapy during the first wave of COVID-19 pandemic.ResultsBetween March 2020 to January 2021, 218 eligible patients undergoing radiation therapy were found for the study. Among the 218 patients, 25 patients (11.47%) were found positive for COVID-19, while 193 patients (88.53%) were negative for COVID-19. Among COVID-19-positive patients, ten patients had < 3 weeks of treatment interruption, while 15 patients had > 3 weeks of treatment interruptions. After recovering from COVID-19, treatment was resumed and completed for 15 (60.00%) of the COVID-19-positive patients. In comparison, 13 patients (52.00%) were lost to follow-up. Three of the COVID-19-positive patients died. The disease was clinically controlled in 12 (48.00%) of the COVID-19-positive patients, and the patients reported locoregional disease progression in 10 (40.00%). Among the 193 COVID-19-negative patients, 32 patients (16.58%) had treatment interruption. Twelve patients (37.50%) had treatment interruptions for less than 1 week. There was a significant difference in the delay of radiation treatment delivery by 2 weeks (11 fractions) in COVID-19-positive patients compared to only two fractions delay in COVID-19-negative patients.ConclusionCOVID-19 impacted the treatment outcomes in both COVID-19-positive and COVID-19-negative cohorts of patients. There was a longer duration of treatment interruptions in the COVID-19-positive patients, leading to fewer patients completing the radiation treatment and thereby increased locoregional disease progression. There was a significant difference in the delay in treatment between the two groups.

Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial.

BackgroundSTAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival.MethodsStandard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy. A total of 460 SOC and 230 SOC plus docetaxel were randomly assigned 2:1. Standard survival methods and intention to treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time if non-proportional hazards. mPFS (new metastases, skeletal-related events, or prostate cancer death) had 70% power (α = 0.05) for a hazard ratio (HR) of 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS), and progression-free survival (PFS: mPFS, locoregional progression).ResultsMedian follow-up was 6.5 years with 142 mPFS events on SOC (3 year and 54% increases over previous report). There was no good evidence of an advantage to SOC plus docetaxel on mPFS (HR = 0.89, 95% confidence interval [CI] = 0.66 to 1.19; P = .43); with 5-year mPFS 82% (95% CI = 78% to 87%) SOC plus docetaxel vs 77% (95% CI = 73% to 81%) SOC. Secondary outcomes showed evidence SOC plus docetaxel improved FFS (HR = 0.70, 95% CI = 0.55 to 0.88; P = .002) and PFS (nonproportional P = .03, restricted mean survival time difference = 5.8 months, 95% CI = 0.5 to 11.2; P = .03) but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95% CI = 0.64 to 1.21; P = .44). There was no evidence SOC plus docetaxel increased late toxicity: post 1 year, 29% SOC and 30% SOC plus docetaxel grade 3-5 toxicity.ConclusionsThere is robust evidence that SOC plus docetaxel improved FFS and PFS (previously shown to increase quality-adjusted life-years), without excess late toxicity, which did not translate into benefit for longer-term outcomes. This may influence patient management in individual cases.

Radiothérapie des cancers du col de l'utérus de stade IVA dans le service de Radiothérapie de l'Hôpital Aristide le Dantec de Dakar

INTRODUCTION: The management of stage IVA cervical cancer is based on radio-chemotherapy followed by utero-vaginal brachytherapy. In this study, we evaluate the results of external radiotherapy on stage IVA cervical cancer. MATERIALS AND METHODS: This was a retrospective, descriptive study. It covered all patients with stage IVA carcinoma of the cervix who received external radiotherapy at the Joliot Curie Institute of the Aristide Le Dantec Hospital from January 2018 to December 2019. RESULTS: We found 164 clinical records of patients, of which 24 patients had stage IVA, (14.3% of all cases). The average age of our patients was 51 years ± 12.13. Seventeen patients (70.9%) had an altered general condition on admission. The predominant histological type was squamous cell carcinoma found in 22 cases (91.6%). Anemia was found in 14 patients, (58.4%). Neo-adjuvant chemotherapy was performed in 21 of our patients (87.5%). Radiotherapy was exclusive in 20 patients (83.3%) and concomitant radio-chemotherapy was performed in 4 patients (16.7%). Normo-fractionated radiotherapy with curative intent was performed in 13 patients (54.2%), and hypo-fractionated radiotherapy with palliative intent was performed in the other 11 patients (45.8%). An objective response was found in 17 cases (70.8%) including 8 in patients who received hypo-fractionated radiotherapy and 9 in patients treated with normo-fractionated radiotherapy at a curative dose. Five patients (20.8%) had acute toxicity and 7 (29.2%) late toxicity. After 3 years of follow-up, 5 patients (29.2%) had loco-regional progression, 9 patients (37.5%) presented loco-regional recurrence and 4 patients (16.7%) presented distant metastases. Overall survival was 26.8% at 3 years. CONCLUSION: Normo-fractionated radiotherapy does not seem superior to palliative hypo-fractionated radiotherapy in terms of clinical response in stage IVA cervical cancer. KEYWORDS: Carcinoma; Uterine cervix; External radiotherapy.

Primary Cardiac Sarcoma of the Left Atrium, A Case Report and Literature Review

Primary malignant cardiac tumours are extremely rare. They count for a quarter of all possible cardiac tumors, and are mostly sarcomas. For a long time, their diagnosis was made post mortem, and they were only reported through autopsy series. Since then, diagnostic and therapeutic advances have been made, making clinical diagnosis of this entity more accessible ante mortem. Nevertheless, due to their rarity, cardiac sarcomas suffer from a lack of therapeutic guidelines. Their treatment is modelled on that of sarcomas developed in other organs of the body. We report an interesting case of a 74-year-old female patient operated on for an infiltrating sarcomatous tumour of the left atrium revealed by dyspnoea associated with cardiac palpitations. Thoracic angioscan and transthoracic echocardiography led to the diagnosis of a cardiac tumour, and the thoracic-abdominal-pelvic Computed Tomography (CT) scan did not reveal any other extracardiac lesions except for a minimal non-neoplastic bilateral pleural effusion. The patient underwent an incomplete surgical procedure with R2 resection followed by adjuvant chemotherapy with doxorubicin monotherapy. The evolution under this treatment was marked by a locoregional progression of the disease with further progression in the atria, mediastinum and dorsal spine after 4 courses. A second line of chemotherapy with Dacarbazine monotherapy was initiated, but the patient died shortly after receiving two courses of the new treatment.

Predictors of Outcome after (Chemo)Radiotherapy for Node-Positive Oropharyngeal Cancer: The Role of Functional MRI.

Simple SummaryWe have conducted a prospective study on patients with locally advanced oropharyngeal cancer who are candidates for concomitant radio-chemotherapy; we considered their anamnestic findings, tumor characteristics and evaluated the role of innovative radiological features, particularly the magnetic resonance imaging (MRI) biomarkers. Our aim was to identify those elements correlated with worse tumor control. Diffusion-weighted (DWI) imaging and dynamic contrast–enhanced (DCE) can help identify hypoxic regions in head and neck cancer which are known to be more resistant to the effects of radiation. A better understanding of these factors may help us improve our knowledge on tumor behavior and thus provide a more tailored treatment in patients that respond poorly.The prognosis of a subset of patients with locally advanced oropharyngeal cancer (LA-OPC) is still poor despite improvements in patient selection and treatment. Identifying specific patient- and tumor-related factors can help to select those patients who need intensified treatment. We aimed to assess the role of historical risk factors and novel magnetic resonance imaging (MRI) biomarkers in predicting outcomes in these patients. Patients diagnosed with LA-OPC were studied with diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline and at the 10th radiotherapy (RT) fraction. Clinical information was collected as well. The endpoint of the study was the development of disease progression, locally or distantly. Of the 97 patients enrolled, 68 were eligible for analysis. Disease progression was recorded in 21 patients (11 had loco-regional progression, 10 developed distant metastases). We found a correlation between N diameter and disease control (p = 0.02); features such as p16 status and extranodal extension only showed a trend towards statistical significance. Among perfusion MRI features, higher median values of Kep both in primary tumor (T, p = 0.016) and lymph node (N, p = 0.003) and lower median values of ve (p = 0.018 in T, p = 0.004 in N) correlated with better disease control. Kep P90 and N diameter were identified by MRMR algorithm as the best predictors of outcome. In conclusion, the association of non-invasive MRI biomarkers and patients and tumor characteristics may help in predicting disease behavior and patient outcomes in order to ensure a more customized treatment.

172P Long-term follow-up of randomized controlled trial (RCT) of locoregional treatment versus not of the primary tumour in de-novo metastatic breast cancer

We had earlier reported no difference in overall survival (OS) at a median follow up of 26 months of the first RCT comparing loco-regional treatment (LRT) vs not (no LRT) for the primary tumour in women with de novo metastatic breast cancer. We also noted then, a significant improvement in loco-regional progression free survival (PFS) and a significant detriment in distant PFS in LRT arm which reproduced findings of earlier animal experiments.

PET/MR Imaging in Evaluating Treatment Failure of Head and Neck Malignancies: A Neck Imaging Reporting and Data System-Based Study.

PET/MR imaging is a relatively new hybrid technology that holds great promise for the evaluation of head and neck cancer. The aim of this study was to assess the performance of simultaneous PET/MR imaging versus MR imaging in the evaluation of posttreatment head and neck malignancies, as determined by its ability to predict locoregional recurrence or progression after imaging. The electronic medical records of patients who had posttreatment PET/MR imaging studies were reviewed, and after applying the exclusion criteria, we retrospectively included 46 studies. PET/MR imaging studies were independently reviewed by 2 neuroradiologists, who recorded scores based on the Neck Imaging Reporting and Data System (using CT/PET-CT criteria) for the diagnostic MR imaging sequences alone and the combined PET/MR imaging. Treatment failure was determined with either biopsy pathology or initiation of new treatment. Statistical analyses including univariate association, interobserver agreement, and receiver operating characteristic analysis were performed. There was substantial interreader agreement among PET/MR imaging scores (κ = 0.634; 95% CI, 0.605-0.663). PET/MR imaging scores showed a strong association with treatment failure by univariate association analysis, with P < .001 for the primary site, neck lymph nodes, and combined sites. Receiver operating characteristic curves of PET/MR imaging scores versus treatment failure indicated statistically significant diagnostic accuracy (area under curve range, 0.864-0.987; P < .001). Simultaneous PET/MR imaging has excellent discriminatory performance for treatment outcomes of head and neck malignancy when the Neck Imaging Reporting and Data System is applied. PET/MR imaging could play an important role in surveillance imaging for head and neck cancer.

Abstract ES9-1: Local therapy of the primary tumor in de novo Stage IV breast cancer

Abstract Background: Distant metastases are present in 6% or more of newly diagnosed breast cancer patients, worldwide. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival and local control, based on multiple retrospective studies, but clinical trials have reported conflicting results. Methods: All four completed trials included women presenting with metastatic breast cancer and an intact primary tumor. The trial design mandated initial systemic therapy prior to randomization in two trials (EA2108 and Tata Memorial) with subsequent randomization to locoregional therapy (LRT) or not, if there was no progression. In two other trials (MF 07-01 and POSYTIVE) randomization occurred upfront. LRT consisted of surgery and radiotherapy per standards applied to patients with non-metastatic disease, with minor differences between trials. The primary endpoint was two or three year overall survival in all four trials, with locoregional control and quality of life as secondary endpoints. Progression-free survival was also examined. The randomized sample size ranged from 93 to 350 across the trials (the POSYTIVE trial did not reach full accrual). Tumor characteristics were balanced between arms, except MF 07-01, which favored the LRT arm. Prospectively measured quality of life (QoL) outcomes have been reported for POSYTIVE and EA2108, assessed using standard instruments. Results. The design, accrual, and main results of the four completed trials, and one still in follow-up (Shien, JCOG 1017) are shown in the Table. Median follow-up duration at the time of reporting ranges from 23 to 53 months in these trials. The overall survival in three of four trials shows no advantage with the use of LRT. MF 07-01 is an outlier, with improved 5-year OS in the LRT arm. Of note, survival rates vary across the trials, depending on the resource environment; in the Tata (India) trial this was 20 months at 2 years, and in EA2108 (USA and Canada) it was 53.1 months (95% CI: 47.9,-) in the systemic therapy arm and 54.9 months (95% CI: 46.7,-) in the locoregional therapy arm. Locoregional progression rates were significantly lower in those randomized to primary site LRT, with locoregional progression occurring in less than 20% of patients treated with LRT with systemic therapy. However, in the systemic therapy alone arms, a minority of patients (under 20%) required palliative LRT, demonstrating the efficacy of contemporary systemic therapy in avoiding symptomatic locoregional progression. Despite the improved local control however, quality of life measures were largely similar between arms in the two trials where prospective, preplanned evaluation of these parameters has been reported (POSYTIVE and EA2108). Conclusions: The preponderance of current evidence does not support use of early locoregional therapy for the primary site as a means to improve survival in patients presenting with metastatic breast cancer. However, LRT was associated with improved locoregional disease control, albeit with no overall impact on quality of life. Questions remain regarding the survival value of primary site LRT in the oligometastatic setting, since this aspect has not been prospectively examined in any existing trial. Phase III trials testing primary site local therapy in de novo Stage IV breast cancersystemic therapy firstAccrual period.Randomized NOverall survival HR (95% CI)Locoregional progression-free survivalBadwe (India)Yes2005-123501.04 (0.84, 1.34)0.16 (0.10, 0.26)Khan (USA &amp; Canada)Yes2011-152561.11 (0.82, 1.52)0.35 (0.21, 0.57)Shien (JapanYes2011-16407Not reportedNot reportedSoran (Turkey)No2008-122740.66 (0.49, 0.88)1% vs. 11%Fitzal (Austria)No2010-19930.69 (0.36, 1.33)8.9% vs. 17.8% Citation Format: S Khan. Local therapy of the primary tumor in de novo Stage IV breast cancer. [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES9-1.

Re‐irradiation of canine non‐lymphomatous nasal tumours using stereotactic radiation therapy (10 Gy x 3) for both courses: Assessment of outcome and toxicity in 11 dogs

No uniformly beneficial treatments exist for dogs with non‐lymphomatous nasal tumours (NLNT) that relapse after radiotherapy (RT). Reirradiation may prolong survival and improve quality of life. In this retrospective study, we describe outcomes for 11 dogs that had CT‐confirmed locoregional progression of NLNT after an initial course of stereotactic RT (SRT#1; 10 Gy × 3) and were then re‐treated with the same type of protocol (SRT#2, also 10 Gy × 3). The median time between SRT #1 and SRT #2 was 243 days (95% CI: 78–385 days). Ten dogs (91%) had a clinical benefit after SRT#1; five dogs (45%) had clinical benefit after SRT#2. Adverse events after SRT#2 included nasocutaneous or oronasal fistula formation (N = 3 at 180, 270, and 468 days), seizures (N = 2 at 78 and 330 days), bacterial or fungal rhinitis (N = 2 at 240 and 385 days), and facial swelling (N = 1 at 90 days). All 11 dogs have died, due to disease progression, presumed radiotoxicity, or declining quality of life; in most cases, it was difficult to discern between these conditions. The median overall survival time (OST) from SRT#1 was 745 days (95% CI: 360–1132). The median overall survival time (OST) from SRT #2 was 448 days (95% CI: 112–626). For these dogs, survival was prolonged, but adverse events after SRT#2 were common (8/11; 73%). Therefore, before consenting to re‐irradiation with this protocol, pet owners should be counselled about survivorship challenges, including risk for severe toxicities, and persistence of clinical signs.

Clinical outcomes of thyroid tumours with concurrent epithelial and mesenchymal components in 14 dogs (2006-2020).

BackgroundWhile rare, multiple individual case reports have described mixed thyroid tumours in dogs containing both epithelial and mesenchymal neoplastic components.ObjectivesIn this retrospective case series, we describe the clinical presentation, treatment and outcome of 14 dogs of canine thyroid tumours with concurrent mesenchymal and epithelial neoplastic populations.MethodsFourteen cases were retrospectively abstracted from nine institutions. Histopathologic samples and reports were collected from 10/14 dogs and reviewed by a single board‐certified anatomic pathologist.ResultsAll 14 dogs had curative‐intent surgery to remove the thyroid neoplasm. The most common surgery performed was a unilateral thyroidectomy (10/14 dogs). Postoperatively, systemic therapy was administered in eight dogs. Six dogs developed local recurrence with a median time to loco‐regional recurrence of 53 days. Ten dogs developed metastatic disease with the most common metastatic site being the lungs (6/10 dogs), with a median time to metastasis of 93 days. Ten dogs were euthanised due to locoregional or distant progression of their mixed thyroid neoplasm. The overall median survival time was 156 days (95%CI: 49–244). The median survival time for dogs treated with adjuvant therapy was 189 days (95%CI: 24–244), whereas dogs without adjuvant therapy had a median survival time of 156 days (95%CI: 35‐upper limit could not be calculated; p = 0.62).ConclusionThe thyroid tumours with both mesenchymal and epithelial components in this small sample set were associated with a poor prognosis after surgical excision with or without adjunctive therapy.

Additive Intralesional Interleukin-2 Improves Progression-Free Survival in a Distinct Subgroup of Melanoma Patients with Prior Progression under Immunotherapy.

Simple SummaryDespite the immense progress in systemic treatment of advanced unresectable melanoma with immunotherapies, there is still an unmet need for patients showing primary resistance. We show that addition of intratumoral injections of the immune modulator Interleukin-2 can overcome primary resistance in a distinct subset of patients and this effect is associated with an intratumoral increase of certain inflammatory cells supporting the paradigm of turning a “cold” into a “hot” tumor.A considerable amount of melanoma patients show primary resistance to PD-1 and CTLA-4 inhibitors. We have previously reported a beneficial role of intralesional Interleukin-2 (IL-2) in 9 melanoma patients developing new locoregional metastases under immunotherapy. We have now expanded this retrospective cohort to 27 patients. Patients were evaluated for their tumor characteristics, treatment response and progression-free and overall survival (PFS/OS). In 16 patients, tumor biopsies before and under IL-2 treatment were evaluated for immune markers. The median follow-up time was 16 (1–59) months from start of IL-2 treatment. Treatment response of locoregional metastases was seen in 74% of all patients and response of distant organ metastases in 37% of stage IV patients, respectively. A prolonged PFS and OS was significantly associated with absence of active distant metastases (p = 0.008), response of locoregional metastases (p = 0.002), increase of absolute eosinophil count (AEC) (p < 0.001) and an influx of CD8+ tumor infiltrating lymphocytes (TILs) (p = 0.003). Additional intralesional treatment with IL-2 in patients with locoregional progression under immunotherapy is a well-tolerated, easily feasible therapeutic option especially in patients lacking active distant metastases. A careful patient selection can lead to an improved PFS and OS.

Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108).

Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results. Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments. Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms. Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.

Radiotherapy for locally advanced unresectable gallbladder cancer - A way forward: Comparative study of chemotherapy versus chemoradiotherapy.

For nonmetastatic locally advanced gallbladder cancer (LAGBC) which remains unresectable and nonmetastatic after chemotherapy, there is no consensus on whether to continue chemotherapy or add local radiotherapy (RT) for improving outcomes. Forty-five patients of surgically unresectable nonmetastatic LAGBC were analyzed. Twenty patients did not receive RT (no RT cohort) and received only chemotherapy, while 25 patients received RT (RT cohort) with conformal techniques along with concurrent gemcitabine-based chemotherapy. No RT and RT cohorts were compared for disease-related outcomes and toxicities. Median follow-up of the entire cohort was 11.5 months. Two-year progression-free survival (18.6% vs. 0%, P = 0.0001) and overall survival (37.3% vs. 5%, P = 0.0001) were significantly better in the RT cohort as compared to a no RT cohort. More number of patients had locoregional progression in the no RT cohort (85% vs. 32%, P = 0.0002). Radiation-induced acute and late gastrointestinal toxicity ≥ RTOG Grade 3 were seen in one and two patients, respectively. Addition of local RT to chemotherapy improves the survival outcomes and can be considered as a definite treatment modality for nonmetastatic LAGBC patients not amenable to surgery who have responded to chemotherapy.