Locoregional Radiotherapy Research Articles

The efficacy of locoregional radiotherapy plus chemotherapy vs. chemotherapy alone in metastatic nasopharyngeal carcinoma: a meta-analysis.

The role of locoregional radiotherapy (LRT) of the nasopharynx and neck in patients with metastatic nasopharyngeal carcinoma (M-NPC) remains unclear. The present meta-analysis aimed to compare the efficacy of chemotherapy (CT) plus LRT with CT alone in M-NPC patients. Eligible manuscripts were searched in the following electronic databases: Cochrane Library, Embase, and PubMed. The hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS), and the risk ratio (RR) of the objective response rate (ORR) and disease control rate (DCR) were pooled and expressed with the 95% confidence intervals (CIs). The analysis was conducted using Review Manager and Stata software. In total 15 retrospective studies and 1 randomized controlled trial were identified comparing 3,402 M-NPC patients of whom 1,387 received CT alone and 2,015 were treated with CT plus LRT. The adjusted HR of OS for CT plus LRT compared with CT alone was 0.45 (95% CI: 0.40-0.52), while the pooled HR of PFS was 0.37 (95% CI: 0.29-0.49). The pooled RR of ORR and DCR for CT plus LRT compared with CT alone was 0.60 (95% CI: 0.46-0.79) and 0.77 (95% CI: 0.71-0.85), respectively. Heterogeneity or publication bias in the studies was not found to have altered the conclusion. For patients with M-NPC, CT + LRT is superior to CT alone providing the higher OS, PFS, ORR, and DCR compared with CT alone. CT combined with LRT should be recommended as a more suitable choice for M-NPC patients.

Radiotherapy for Post-Chemotherapy Residual Mass in Advanced Seminoma: A Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography-Based Risk-adapted Approach

AimsThere is a lack of consensus regarding the management of post-chemotherapy residual mass in classical seminoma. The use of fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) may aid the detection of residual masses harbouring viable disease and help to tailor therapy. The aim of this study was to evaluate if PET-CT could identify patients who will benefit from locoregional radiotherapy. Materials and MethodsThis ethics-approved study included patients with advanced classical seminoma primarily treated with standard platinum-based first-line chemotherapy. Patients were either observed or given adjuvant radiotherapy based on the clinician's preference and followed up. For this study, patients were stratified into two groups based on FDG PET-CT residual nodal maximum standardised uptake value (SUVmax): low risk (SUVmax <3) and high risk (SUVmax ≥3). Further subgroup analysis was carried out for patients with residual nodal size ≥3 cm and SUVmax ≥3, and this was considered as the very high risk group. The diagnostic accuracy of FDG PET-CT was assessed and survival was compared between the different groups. ResultsSixty-nine patients were included in the study: 48 patients were observed and 21 received radiotherapy. The low and high risk groups contained 50.7% and 49.3% of the patients, respectively. The very high risk subgroup had 24 patients. At a median follow-up of 44 months, locoregional failures in the radiotherapy and observation cohorts were 0% and 30% (P = 0.059) in the very high risk subgroup and 5.8% and 29.4% (P = 0.078) in the high risk group. The positive predictive value for the very high risk and high risk groups was 30% and 17.1%, respectively. The benefit of locoregional control failed to translate into overall survival benefit. ConclusionA tailored, FDG PET-based risk-adapted treatment approach can refine the management of post-chemotherapy residual masses in seminoma. In this study, with the largest cohort of advanced seminoma patients treated with radiotherapy reported to date, radiotherapy seems to benefit patients with post-chemotherapy residual mass SUVmax ≥3.

Abstract GS2-03: Prime 2 randomised trial (postoperative radiotherapy in minimum-risk elderly): Wide local excision and adjuvant hormonal therapy +/- whole breast irradiation in women =/&amp;gt; 65 years with early invasive breast cancer: 10 year results

Abstract Background: There is limited level 1 evidence on the long term outcomes after loco-regional radiotherapy after breast conserving surgery (BCS) in older patients when they are also receiving appropriate systemic therapy. Practice and guidelines vary. PRIME 2 is an international phase 3 RCT designed to address this specific question. Methods: From April 2003 to December 2009, 1326 patients were randomised to receive (n=658) or not receive (n=668) whole breast radiotherapy (RT). Eligible patients were aged ≥ 65 years, T1-2 (up to 3cm) NO, MO, hormone receptor positive, clear excision margins (minimum 1mm), axillary node negative (pNO) receiving adjuvant hormonal therapy. Patients were eligible if they had grade 3 tumours or lymphovascular invasion but not both. The target accrual was 1300 patients based on detecting a difference in local recurrence rates between 5% in the no RT arm and 2% in the RT arm at 5 years, with 80% power and 5% significance. Ipsilateral breast tumour recurrence (IBTR) was the primary endpoint. Secondary endpoints were regional recurrence, contralateral breast cancer, distant metastases and overall survival. Results: Median follow up is 7.3 years. At 10 years IBTR was 9.8% (95% CI 6.5, 13.2%) in the no RT arm and 0.9% (95% CI 0.1, 1.6%) in the RT arm. The hazard ratio for IBTR for those receiving RT was 0.12 (95% CI 0.05, 0.31)(p&amp;lt;0.0001). Significant differences were found in regional recurrence (2.3% no RT vs 0.5% RT (p=0.014), but not in contralateral breast cancer (1.0% no RT, 2.2% RT, p=0.20) or distant metastases (1.4% no RT, 3.6% RT, p=0.07). Breast cancer free survival was 12.7% (95% CI 9.1, 16.2%) for the no RT arm and 6.6% (95% CI 4.1, 9.1%) for the RT arm. Breast specific survival: no RT 98.2% (95% CI 96.9, 99.4%; RT 97.8% (95% CI 96.0,99.5%) p=0.91. Overall survival at 10 years was 80.4% (95% CI 76.4, 84.5%) without RT and 81.0% (95% CI 76.7, 85.3%) with RT (p=0.68), with most deaths (80/88 no RT vs 76/79 RT) not linked to breast cancer recurrence with no influence of RT (p=0.17). Causes of death are shown in Table. Conclusions: 10 year follow data from the PRIME 2 trial shows that the omission of RT after BCS in women aged ≥ 65 years with T1-2, pN0 hormone receptor positive breast cancer results in only 9.8% IBTR. While this rate is significantly reduced by RT (to 0.9%), the absolute reduction is modest, and there were no differences in the secondary endpoints of distant metastases, contralateral breast cancer or overall survival and a small but significant difference in regional recurrence. These data suggest that postoperative radiotherapy in this patient group who are receiving adjuvant hormonal therapy does not impact on overall survival in the context of modern approaches to local and systemic adjuvant therapy, with most patients in both arms dying of causes unrelated to breast cancer or its treatment. Cause of deathNo RTRTTotalCancer25 (28%)29 (37%)54Of which breast cancer8 (9%)3 (4%)11Cardio-vascular9 (10%)14 (18%)23Other/unknown54 (61%)36 (45%)90Total8879167 Citation Format: Ian H Kunkler, Linda J Williams, Wilma Jack, David A Cameron, Michael Dixon. Prime 2 randomised trial (postoperative radiotherapy in minimum-risk elderly): Wide local excision and adjuvant hormonal therapy +/- whole breast irradiation in women =/&amp;gt; 65 years with early invasive breast cancer: 10 year results [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 GS2-03.

Abstract PS15-07: Deep inspiration breath-hold in right-sided breast irradiation: Quantifying the benefit

Abstract Background: Deep inspiration breath-hold (DIBH) in left-sided breast radiation therapy (RT) is proven to reduce ipsilateral lung and heart doses. The potential benefit of this technique in right-sided breast RT has not been fully explored. We describe the differences in organs at risk (OAR) dosimetry between DIBH and free-breathing (FB) plans in 15 patients who received right-sided breast RT. Materials and methods: Fifteen consecutive patients with right-sided breast cancer who received RT with DIBH between January 1, 2016 and August 31, 2019 were enrolled in this study. All patients initially underwent RT planning with FB scans, and subsequently required DIBH rescanning due to concerns related to exposure of OAR. Dose volume histograms (DVH) for the target volume and OAR coverage were compared between both plans on RayStation Treatment Planning System to quantify the benefit of DIBH. The median value of relative reduction (MRR) and interquartile range in dosimetric parameters were calculated when comparing DIBH to FB. Two-sided Wilcoxon signed-rank test was performed, and a p-value &amp;lt; 0.05 was considered statistically significant. Results: The median age of patients was 64 (38-78). None of the patients had cardiac, respiratory or hepatic comorbidities. The majority of patients (10/15) received locoregional RT (50 Gy in 25 fractions); the remaining 5 patients received breast RT (42.4 Gy in 16 fractions). Tumor bed boost was delivered in 9 of 15 patients. DIBH was delivered throughout RT to 14/15 patients and the clinical goal(s) for which DIBH was introduced was achieved in all cases. DIBH was most commonly used to minimize liver exposure (11/15 patients); in 3 of these 11 patients, reduction in heart or lung exposure was also required. Statistically significant reductions in the imaged liver V5Gy [MRR 89.8% (99 to 71.6, p&amp;lt;0.001)], V10Gy [MRR 94.7% (100 to 77.9, p&amp;lt;0.001)], V20Gy [MRR 97.2% (100 to 84.7, p&amp;lt;0.001)], maximum dose [MRR 15.5% (73.2 to 8, p&amp;lt;0.001)] and average dose [MRR 68.7% (79.4 to 58.6, p&amp;lt;0.001)] were observed with DIBH. Compared to FB, the use of DIBH led to statistically significant reductions in right lung V20 [Median Relative Reduction 20.8% (27.1 to 15.9, p&amp;lt;0.001)], as well as the maximum dose received by the heart and left lung. The target volume coverage was not compromised by DIBH, with at least 99% of the target volume receiving 95% dose in all 15 cases. Conclusion: DIBH for right-sided breast irradiation effectively reduces exposure to liver, lung and heart while maintaining target volume coverage. It can be employed to achieve specific dosimetric goals in the clinical setting. Citation Format: Revathy Krishnamurthy, Grace Lee, Zhihui (Amy) Liu, Tyler Pittman, Anthony Fyles, Christine Anne Koch. Deep inspiration breath-hold in right-sided breast irradiation: Quantifying the benefit [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 PS15-07.

Voluntary versus ABC breath-hold in the context of VMAT for breast and locoregional lymph node radiotherapy including the internal mammary chain

BackgroundDeep-inspiration breath-hold (DIBH) reduces radiation dose to the heart in patients undergoing locoregional breast radiotherapy. In the context of tangential irradiation of the breast/ chest wall, a voluntary breath hold (vDIBH) technique has been shown to be as reproducible as a machine-assisted breath hold technique using the active breathing co-ordinator (ABC™, Elekta, Crawley, UK, ABC_DIBH). This study compares set-up reproducibility for vDIBH versus ABC_DIBH in patients undergoing volumetric-modulated arc radiotherapy (VMAT) for breast cancer, both with and without wax bolus. MethodPatients with breast cancer requiring pan regional lymph node VMAT +/− wax bolus in breath-hold were CT scanned in vDIBH and ABC_DIBH. Patients were randomised to receive one technique for fractions 1–7 and the other for fractions 8–15. Daily cone beam computed tomography (CBCT) was performed and registered to planning-CT using bony anatomy. Within-patient comparisons of mean daily chest wall position were made using a paired t-test. Population, systematic (∑) and random errors (α) were estimated. Intrafraction reproducibility was assessed by comparing chest wall position and diaphragm movement between consecutive breath holds on CBCT. Results16 patients were recruited. All completed treatment with both techniques (9 patients with wax bolus, 7 patients without). CBCT derived ∑ were 2.1–6.4 mm (ABC_DIBH) and 2.1–4.9 mm (vDIBH), α were 1.7–2.6 mm (ABC_DIBH) and 2.2–2.7 mm (vDIBH) and mean daily chest wall displacements (MD) were 0.0–1.5 mm (ABC_DIBH) and -0.1–1.6 vDIBH (all p non-significant). Chest wall and diaphragm position was equivalent between consecutive breath holds in ABC and vDIBH (median difference 1.0 mm and 0.8 mm respectively, non p significant) demonstrating equivalent intrafraction reproducibility. ConclusionThis study demonstrates that a simple voluntary breath hold technique is feasible in combination with VMAT (+/− bolus) and is as reproducible as ABC_DIBH with VMAT for the irradiation of the breast and axillary and IMC lymph nodes in breast cancer patients.

Selection criteria for early breast cancer patients in the DBCG proton trial – The randomised phase III trial strategy

Background and purposeAdjuvant radiotherapy of internal mammary nodes (IMN) improves survival in high-risk early breast cancer patients but inevitably leads to more dose to heart and lung. Target coverage is often compromised to meet heart/lung dose constraints. We estimate heart and lung dose when target coverage is not compromised in consecutive patients. These estimates are used to guide the choice of selection criteria for the randomised Danish Breast Cancer Group (DBCG) Proton Trial. Materials and methods179 breast cancer patients already treated with loco-regional IMN radiotherapy from 18 European departments were included. If the clinically delivered treatment plan did not comply with defined target coverage requirements, the plan was modified retrospectively until sufficient coverage was reached. The choice of selection criteria was based on the estimated number of eligible patients for different heart and lung dose thresholds in combination with proton therapy capacity limitations and dose–response relationships for heart and lung. ResultsMedian mean heart dose was 3.0 Gy (range, 1.1–8.2 Gy) for left-sided and 1.4 Gy (0.4–11.5 Gy) for right-sided treatment plans. Median V17Gy/V20Gy (hypofractionated/normofractionated plans) for ipsilateral lung was 31% (9–57%). The DBCG Radiotherapy Committee chose mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37% as thresholds for inclusion in the randomised trial. Using these thresholds, we estimate that 22% of patients requiring loco-regional IMN radiotherapy will be eligible for the trial. ConclusionThe patient selection criteria for the DBCG Proton Trial are mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37%.

A phase II study of atezolizumab (ATEZO) and bevacizumab (Bev) in combination with Y90 TARE in patients (Pts) with hepatocellular carcinoma (HCC).

TPS358 Background: The anti–PD-L1 antibody ATEZO prevents PD-L1 from interacting with PD-1 and B7.1, thus reinvigorating antitumor T cell activity. Anti-VEGF BEV can increase dendritic cell maturation, enhance T cell infiltration, and reduce myeloid-derived suppressor cells and regulatory T-cells in tumors. This combination has been FDA approved for first-line treatment of advanced HCC based on the IMbrave 150 study. On the other hand, locoregional radiotherapy (e.g., Y90 TARE) enhances the diversity of the intratumoral T cell receptor repertoire. It is the standard of care for pts with intermediate-stage HCC (iHCC). Based on preclinical and clinical data, we hypothesize that the combination of Y90 TARE, BEV, and ATEZO induces synergistic tumor-killing. Methods: This is an open-label, multicenter, randomized phase II study of Y90 TARE and BEV plus ATEZO compared with Y90 TARE alone in pts with unresectable IHCC. The primary study objective is to assess and compare the progression-free survival (PFS) (per mRECIST 1.1) of pts in each arm. The main secondary objective is to determine the safety and tolerability (CTCAE v5) of TARE combined with ATEZO and BEV in pts with HCC. Exploratory objectives are to assess the role of the immunoscore and PD-L1 expression levels in the prediction of improved clinical outcome in pts receiving Y-90 TARE and BEV plus ATEZO; the composition of tumor-infiltrating immune cell subtypes in predicting response to a chosen therapy; how Y90 therapy affects the proportion of antigen-presenting cells in the tumor; and symptoms experienced by pts receiving TARE and BEV plus ATEZO treatment, using patient-reported outcomes. Eligible pts have either HCC that is not amenable to surgical resection, confirmed by pathology review, or at least BCLC stage B HCC outside of downstaging criteria. Other standard eligibility criteria apply. Pts must have a pretreatment liver biopsy taken and then be randomized 1:1 to TARE (Arm A) or TARE followed by ATEZO and BEV (Arm B). Pts will have TARE mapping during week (wk) 1 and TARE treatment during wk 2. In Arm B, pts will start BEV plus ATEZO 4 wks (±1 wk) after TARE treatment. Pts will have abdominal MRI or CT scans every 12 weeks, CT scans of the chest every 24 wks, and a second tumor biopsy at 4 wks. Disease progression will be captured by both RECIST 1.1 and mRECIST. We plan to assess the safety of TARE with BEV and ATEZO in the first 10 pts randomized to Arm B for two cycles. If there are no grade ≥ 3 unexpected toxicities possibly, probably or definitely related to combined TARE plus BEV plus ATEZO, the study will continue to accrue 128 pts in total. Pts will continue study treatment (Arm B) for a total of 24 months from initiation of TARE or until intolerable toxicity or disease progression occur, whichever is earlier. Enrollment began in September 2020. Clinical trial information: NCT04541173.

Patient-Reported Pain in Patients with Breast Cancer Who Receive Radiotherapy

BackgroundPatients who receive radiation treatment (RT) for breast cancer often report pain, which contributes negatively to quality of life (QoL). AimsTo identify demographic, treatment, and disease characteristics associated with pain and changes in pain before and after RT using the Edmonton Symptom Assessment Scale (ESAS). DesignRetrospective study. SettingsOdette Cancer Centre. ParticipantsPatients diagnosed with nonmetastatic breast cancer from January 2011-June 2017 with at least one ESAS completed pre-RT and one completed post-RT. MethodsData on systemic treatment, radiation, patient demographics, and disease stage were extracted. To identify factors associated with pain before and after RT and changes in pain, univariate and multivariate general linear regression analysis were conducted. p < .05 was considered statistically significant. ResultsThis study included 1,222 female patients with a mean age of 59 years. ESAS was completed an average of 28 days before RT (baseline) and 142 days after RT, respectively. In multivariable analysis, higher baseline pain scores were associated with having recently completed adjuvant chemotherapy (p = .002) and eventual receipt of locoregional (p = .026) or chest wall (p = .003) radiation. Adjuvant chemotherapy (p = .002) and chest wall radiation (p = .03), were associated with a significant reduction in pain score after radiotherapy, while locoregional RT was associated with a higher pain score after RT (p < .001). ConclusionsPatients with locoregional RT had higher baseline pain that remained elevated after RT completion and should be screened for pain and provided with pain management and support when necessary.

Prognostic model for risk stratification of de novo metastatic nasopharyngeal carcinoma patients treated with chemotherapy followed by locoregional radiotherapy

BackgroundThere is no clinically applicable prognostic model designed for patients with de novo metastatic nasopharyngeal carcinoma (mNPC) treated with chemotherapy followed by locoregional radiotherapy (LRRT). We sought to develop a predictive tool of overall survival for individualized prediction and risk stratification in this heterogeneous patient population.Patients and methodsA total of 244 eligible patients with de novo mNPC, who were treated with platinum-based first-line chemotherapy followed by LRRT, were included in this retrospective study. We divided patients into the training and validation sets based on the date of initial treatment, with 152 patients treated between 2008 and 2013 comprising the training set for model development and 92 patients treated at a later time (2014 to 2015) forming the validation set. We applied Cox proportional hazards model to examine factors associated with overall survival (OS). We developed and subsequently validated a prognostic model to predict OS. We assessed the performance of this prognostic model and stratified patients based on prognostic scores obtained from this proposed model.ResultsThe median OS of the entire cohort was 60.9 months. C-creative protein, number of metastatic sites, liver metastasis, post-treatment Epstein–Barr virus DNA, and response of metastasis were significantly associated with OS. A prognostic model for individual survival prediction was developed and graphically represented as a nomogram. The model showed favorable discrimination (C-index: 0.759), predictive accuracy [time dependent area under the curve (tAUC) at 5 years: 0.800], and calibration, and was further validated in an independent dataset. A risk stratification derived from the model can stratify these patients into three prognostic subgroups with significantly different survival.ConclusionWe developed and validated a prognostic model that exhibited adequate performance in individualized prediction and risk stratification for patients with de novo mNPC treated with chemotherapy followed by LRRT.

Insights into the theranostic value of precision medicine on advanced radiotherapy to breast cancer.

Breast cancer is the most common cancer in women worldwide. “Breast cancer” encompasses a broad spectrum of diseases (i.e., subtypes) with significant epidemiological, clinical, and biological heterogeneity. Each of these subtypes has a different natural history and prognostic profile. Although tumour staging (TNM classification) still provides valuable information in the overall management of breast cancer, the current reality is that clinicians must consider other biological and molecular factors that directly influence treatment decision-making, including extent of surgery, indication for chemotherapy, hormonal therapy, and even radiotherapy (and treatment volumes). The management of breast cancer has changed radically in the last 15 years due to significant advances in our understanding of these tumours. While these changes have been extremely positive in terms of surgical and systemic management, they have also created significant uncertainties concerning integration of local and locoregional radiotherapy into the therapeutic scheme. In parallel, radiotherapy itself has also experienced major advances. Beyond the evident technological advances, new radiobiological concepts have emerged, and genomic data and other patient-specific factors must now be integrated into individualized treatment approaches. In this context, “precision medicine” seeks to provide an answer to these open questions and uncertainties. Although precision medicine has been much discussed in the last five years or so, the concept remains somewhat ambiguous, and it often appear to be used as a “catch-all” term. The present review aims to clarify the meaning of this term and, more importantly, to critically evaluate the role and impact of precision medicine on breast cancer radiotherapy. Finally, we will discuss the current and future of precision medicine in radiotherapy.

Is there a role for locoregional treatment of the primary tumor in de novo metastatic breast cancer in the era of tailored therapies?

Biological effects of loco-regional treatment in dnMBC. • LRT of the primary tumor in dnMBC remains steadily proposed by clinicians over decades. • LRT in dnMBC is a shared decision between medical, radiation and surgical oncologists. • LRT should be considered after controlled disease by systemic therapies and must depend on IHC subtypes. • Reassuring data are now available regarding exclusive loco-regional radiation therapy as a means of LRT. Improvements in systemic therapies have changed the face of de novo metastatic breast cancer (dnMBC), with a 5-year survival rate exceeding 25 %. Increasing evidence suggests that a subset of patients could benefit from a locoregional treatment (LRT) with prolonged survival, although the diversity of publications on the subject make it difficult to draw any conclusions. In this review, we summarize the available data on retrospective, prospective and current ongoing clinical trials. Since factors such as tumor biology, pattern of metastatic dissemination and the timing of the treatment are closely linked to the therapeutic strategy, we focus on papers which include these aspects. We discuss recent studies indicating that exclusive radiotherapy provides results comparable with those obtained by surgery. We will then discuss the biological rationale for LRT. Finally, we propose a decision-tree to select the optimal candidates for LRT in dnMBC patients.

Huge B-Cell Lymphoma of the Maxillary Sinus: Case Report and Review of the Litterature

Primary non-Hodgkin’s lymphoma (NHL) of Paranasal sinus is a rare entity with special characteristics; their locations in the air spaces of the face coming in second row. The prognosis depends on tumor stage and extension into the paranasal sinuses We related the case of a primitive NHL located in the maxillary sinus in a patient of 50 years, invading the entire homolateral nasal cavity. The histopathologic interpretation was B cell lymphoma; the patient received 5 adjuvant chemotherapy treatments according to the CHOP protocol, followed by locoregional external radiotherapy and the evolution was favorable after eighteen months follow-up

Effect of breathing motion on robustness of proton therapy plans for left-sided breast cancer patients with indication for locoregional irradiation

Purpose To investigate the dosimetric impact of breathing motion on robustly optimized proton therapy treatment plans for left-sided breast cancer patients with an indication for locoregional irradiation. Materials and methods Clinical Target Volumes (CTVs) (left-sided breast, level 1 to 4 axillary lymph nodes, interpectoral and internal mammary lymph node regions) and organs at risk were delineated on 4 D-CTs of ten female patients. After treatment planning to a prescribed dose of 40.05 Gy(RBE) in 15 fractions on the time-averaged CT, the dose was calculated on all ten phases of the breathing cycle. Robustness to setup (5 mm) and range errors (3%) was evaluated for those ten phases. Correlations were evaluated between the phases of the breathing cycle and the D98% of the CTV and the Dmean of the heart. Results Correlations coefficients were between −0.12 and 0.29. At the most extreme values of the 28 robustness scenarios, the clinical goals were met for all but two patients. The mean heart dose was 0.41 Gy(RBE) with a standard deviation of 0.31 Gy(RBE) of proton therapy plans. Conclusion The effect of breathing motion on the robustness of proton therapy treatment plans for this patient group is minor and not of clinical significance. Based on this patient group, a deep-inspiration breath hold seems to be unnecessary to improve robustness for these patients.

Management and Outcomes of Testicular Lymphoma in the Rituximab Era at an Australian Tertiary Centre

INTRODUCTION Testicular lymphoma accounts for &amp;lt;5% of all testicular neoplasms and 1-2% of non-Hodgkin's lymphoma (NHL). Historically, outcomes for testicular lymphoma have generally been inferior to systemic diffuse large B cell lymphoma (DLBCL) with a higher incidence of central nervous system (CNS) relapse. Although intrathecal methotrexate is currently considered standard of care for testicular lymphoma, there has been significant debate about its efficacy in preventing CNS relapse. Due to the rarity of testicular lymphoma, prospective data in this field is lacking. Our study aims to examine treatment practices and outcomes for all newly diagnosed patients with testicular lymphoma in a large tertiary centre in Australia since the introduction of rituximab. METHODS We conducted a retrospective review of all patients diagnosed with primary testicular lymphoma (PTL) between 2003 and 2019 at the Princess Alexandra Hospital, Brisbane, Queensland, Australia (Human Research Ethics Approval: LNR/2019/QMS/56644). RESULTS During this period, 18 patients were diagnosed with PTL; all patients had DLBCL histology. The median follow-up period for living patients was 6.5 years (range 1.3-13.4 years). The median age was 61.3 years (interquartile range: 58.3 - 71.1 years). All patients were HIV negative. The majority of patients had an Eastern Cooperative Oncology Group (ECOG) score of zero (n = 13; 72.2%) with no B symptoms (n = 14; 77.7%) and a normal LDH (n = 11; 61.1%). 50% of patients had Stage IV disease (Table 1). 17 patients (94.4%) underwent an orchidectomy (unilateral: 16, bilateral: 1) at diagnosis. Following on, as first-line systemic therapy, 14 patients (77.7%) received R-CHOP chemotherapy. Other regimens used were CHOP (n=1), modified HyperCVAD (n=1), R-HyperCVAD (n=1) and R-CVP (n=1). 17 patients (94.4%) received CNS prophylaxis with intrathecal chemotherapy; one patient declined intrathecal therapy and was given high dose intravenous methotrexate instead. 15 (83.3%) patients received loco-regional radiation therapy. Outcomes to first-line treatment were: 13 patients (72.2%) achieved complete remission (CR); one patient (5.5%) achieved partial remission (PR) (Deauville score 4 on interim PET assessment, prompting escalation to salvage therapy); three patients (16.6%) had progressive disease (and were subsequently managed with salvage chemotherapy) and one patient elected for palliation after a single cycle of R-CVP. Among the four patients who received salvage therapy, two patients (50%) achieved CR and two patients had progressive disease and were palliated. Among the 15 patients who achieved CR (n=13 R-CHOP; n=2 salvage chemotherapy), two patients relapsed, and both had CNS involvement (n=1 CNS only relapse; n=1 CNS and systemic relapse). Despite intrathecal prophylaxis, the CNS relapse rate was 12% (n=2/17). Of note, the patient who did not receive intrathecal chemotherapy remained in CR at the date of last follow-up. In total, there were seven deaths. The causes of death were: lymphoma (n=4), treatment-related mortality (n=2) and other (n=1; due to aspiration pneumonia after stroke). The 2-year and 5-year progression free survival (PFS) rates were 77.8% and 52.4%, respectively (Figure 1A). The 2-year and 5-year overall survival (OS) rates were 83.3% and 56.8%, respectively (Figure 1B). CONCLUSION With the practice of R-CHOP, intrathecal prophylaxis for CNS disease and loco-regional radiation therapy, our outcomes are comparable to the literature (5y OS ~50%). Despite intrathecal prophylaxis, our CNS relapse rate was 12%. Better strategies are required to improve the control of systemic disease and reduce the incidence of CNS relapse in patients with testicular lymphoma. Disclosures Mollee: Janssen:Membership on an entity's Board of Directors or advisory committees, Research Funding;BMS/Celgene:Membership on an entity's Board of Directors or advisory committees;Amgen:Membership on an entity's Board of Directors or advisory committees;Takeda:Membership on an entity's Board of Directors or advisory committees;Pfizer:Membership on an entity's Board of Directors or advisory committees;Caelum:Membership on an entity's Board of Directors or advisory committees.

Radiotherapy in Metastatic Oropharyngeal Cancer.

The role of locoregional radiotherapy for metastatic oropharyngeal squamous cell cancer (OPSCC) is unclear. We investigated the impact of head and neck radiotherapy on survival in de novo metastatic OPSCC patients who received systemic therapy. We queried the NCDB from 2004-2015 for metastatic OPSCC patients at diagnosis with known HPV-status who received systemic therapy. The association of head and neck radiotherapy with overall survival was analyzed using the Kaplan-Meier method, Cox proportional hazards model, and propensity score-matched analysis adjusting for demographic and disease-specific prognostic factors. Of the 2,139 patients with metastatic OPSCC who presented with metastases and received systemic treatment, we identified 556 patients with known HPV-status. Among these 556 patients, 49% were HPV-positive and 56% received head and neck radiotherapy. With a median follow-up of 17.5 months (IQR 6.0-163.4 months), radiotherapy was associated with significantly improved 1-year OS (67% vs 58%, log-rank P < .001) which remained significant on MVA (HR 0.78 95% CI 0.62-0.97 P = .029). In HPV-status subgroup analysis, a survival benefit was identified in HPV-positive patients (1-year OS 77% vs 67%, log-rank P < .001) but not in HPV-negative patients. Results were consistent on a propensity score-matched analysis of 212 HPV-positive matched patients (HR 0.66, 95% CI 0.49-0.83, P < .001). The survival of metastatic OPSCC remains limited. In this large series of patients with known HPV-status, head and neck radiotherapy was associated with longer survival in those with HPV-associated disease. These data could guide management of this challenging group of patients for head and neck cancer practitioners. 3 Laryngoscope, 131:E1847-E1853, 2021.

Optimizing the Treatment Pattern for De Novo Metastatic Nasopharyngeal Carcinoma Patients: A Large-Scale Retrospective Cohort Study.

ObjectivesTo investigate the optimal treatment pattern in patients with de novo metastatic nasopharyngeal carcinoma (NPC).MethodsWe assessed 502 consecutive and unselected de novo metastatic NPC patients in Sun Yat-sen University Cancer Center (SYSUCC) from November 2006 to October 2016 in our study. All patients were treated with palliative chemotherapy (PCT) and 308 patients received locoregional radiotherapy (LRRT) subsequently. Our primary study endpoint was overall survival (OS).ResultsThe patients treated with LRRT were associated with improved survival on univariate analysis (3-year OS rate 63.7% vs. 31.8%, P < 0.001) and multivariate analysis (HR 0.52, 95%CI 0.40–0.68, P < 0.001). The overall survival benefit of more than 4 PCT cycles was significant in female (HR 0.45, 95% CI 0.24–0.86, P = 0.016) and patients with multiple metastatic sites (HR 0.42, 95% CI 0.26–0.66, P < 0.001). The application of concurrent chemotherapy (CCT) was not associated with better survival among patients receiving LRRT (HR 1.31, 95% CI 0.92–1.86, P = 0.141).ConclusionLRRT prolonged survival in de novo metastatic NPC. For patients treated with multiple metastatic sites, more than 4 cycles of PCT is necessary. CCT does not improve survival in de novo metastatic NPC patients.

Outcome of Treatment After Locoregional Radiation, Neoadjuvant and Adjuvant Chemotherapy for Breast Cancer

The addition of systemic therapy to locoregional treatment for women with all stages of breast cancer improves survival. Reliable data are lacking about the outcomes of women with breast cancer in low-middle income countries who are treated with a combination of radiotherapy (RT), surgery, and systemic therapy. report the outcome of women with breast cancer treated with either neoadjuvant chemotherapy (NACT) or adjuvant chemotherapy at the National Centre for Radiotherapy and Nuclear Medicine in Accra, Ghana. The medical charts of all women with breast cancer managed at the National Centre for Radiotherapy and Nuclear Medicine from 2005 to 2014 were reviewed. Available patient specific demographic data, tumor stage, treatment sequence, and follow-up information were recorded. Logistic regression was used to estimate the presence of locoregional (LRR) and distant recurrence (DR) between two chemotherapy groups. Overall survival (OS) and disease-free survival (DFS) were used as time dependent outcomes and were analyzed using cox proportional hazard (CPH) model. All the models were adjusted with clinico-pathologic variables and estimates were reported along with their 95% confidence interval (CI). A total of 387 patients with a median follow up of 48 months were included in the study. The median age at diagnosis was 51 years. 49.6% of women had advanced pathologic stage ≥pT3. 58.9% (n = 228) received adjuvant chemotherapy whereas 41.1 % (n = 159) received NACT. The majority of women (94.1%, n = 365) received RT. 18.4% (n = 67) underwent breast conservation therapy followed by RT to a mean dose of 48.8 Gy in 10-30 fractions, and 81.6% (n = 298) had a mastectomy followed by RT to a mean dose of 47.92 Gy in 10-30 fractions. In an adjusted logistic model, no difference was observed in LRR between patients receiving NACT compared to those receiving adjuvant chemotherapy (OR = 1.05, 95% CI {0.44 - 2.47}, p = 0.9). However, NACT recipients had a higher likelihood of DR (OR = 1.97, 95% CI, {1.24 – 3.15}, p = 0.004). In a multivariate analysis, no differences were observed in survival between the two chemotherapy groups (HR = 1.43, 95% CI, {0.91 – 2.26}, p = 0.1). There was a trend towards lower DFS within the NACT group compared to the adjuvant chemotherapy group, with patients receiving NACT having a 52% likelihood of lower DFS (HR = 1.52, 95% CI, {0.96 – 2.39}, p = 0.06). While many women present with late stage disease in Ghana, outcomes after trimodal therapy are comparable to what is observed in developed countries. Advanced stage of disease is significantly associated with recurrence and survival, hence early detection in a resource limited setting is crucial to optimal outcomes. To our knowledge, this is the first and largest study to report on the outcomes of women with breast cancer who receive standard of care treatment in Ghana.

Hypofractionated Versus Conventional Fractionated Loco-Regional Adjuvant Radiation Therapy Breast Cancer After Breast-Conserving Surgery: A Single Institution Retrospective Study

Hypofractionated Versus Conventional Fractionated Loco-Regional Adjuvant Radiation Therapy Breast Cancer After Breast-Conserving Surgery: A Single Institution Retrospective Study

337 Poster - Results of locoregional radiotherapy or axillary dissection in breast cancer with pN0(i+) and pN1mi nodal disease

337 Poster - Results of locoregional radiotherapy or axillary dissection in breast cancer with pN0(i+) and pN1mi nodal disease

Combination of Olaparib and Radiation Therapy for Triple Negative Breast Cancer: Preliminary Results of the RADIOPARP Phase 1 Trial

Preclinical studies have evidenced that triple-negative breast cancer (TNBC) cell lines are more sensitive to poly (ADP-ribose) polymerase inhibitors. This provides a strong rationale for developing a new therapeutic approach for TNBC management based on poly (ADP-ribose) polymerase inhibition. The primary goal of the RADIOPARP phase 1 trial was to evaluate the dose-limiting toxicities (DLT) and the maximum tolerated dose of olaparib combined with locoregional radiation therapy. RADIOPARP was a single institutional phase 1 trial which evaluated olaparib-radiation therapy combination in patients with inflammatory, locoregionally advanced or metastatic TNBC who received neoadjuvant chemotherapy. Radiation therapy delivered 50 Gy to the breast or to the chest wall. Lymph nodes could be included in target volumes according to local guidelines. The dose-finding toxicity-based study was conducted in sequential and adaptive Bayesian scheme using the time-to-event continual reassessment method, with 4 olaparib dose levels (50 mg, 100 mg, 150 mg, and 200 mg twice per day). Twenty-four patients with Eastern Cooperative Oncology Group Performance Status of 0 or 1 were enrolled from September 2017 to November 2019. Twenty-one patients (87.5%) received the olaparib-radiation therapy combination after breast surgery owing to residual disease after neoadjuvant chemotherapy, and the 3 other patients (12.5%) had unresectable tumors which were refractory to neoadjuvant chemotherapy. All patients received full course combination treatment as follows: 4 patients (pts) at 50 mg twice a day, 8 pts at 100 mg twice a day, 7 pts at 150 mg twice a day, and 5 pts at 200 mg twice a day. No DLT was observed. Olaparib was escalated to the maximum target dose of 200 mg twice a day without DLT. Further follow-up is needed to evaluate the late toxicities. Pending the long-term results of the RADIOPARP trial, we suggest using 200 mg of olaparib twice per day for future trials.