Locoregional Progression Research Articles

Radiation therapy for recurrent extrahepatic bile duct cancer.

PurposeMore than half of patients with bile duct cancer (BDC) develop recurrence even after curative resection. Recurrent BDC has a poor prognosis, and no optimal treatment modality has been established. We therefore analyzed our experience on the survival outcomes of radiation therapy (RT) for recurrent extrahepatic bile duct cancer (EHBDC).Patients and methodsWe retrospectively analyzed the records of patients with recurrent EHBDC who underwent concurrent chemoradiation therapy (CCRT) or RT alone at our institution between January 2001 and June 2015. Freedom from locoregional progression (FFLP), progression-free survival (PFS), and overall survival (OS) were assessed, and univariate and multivariate analyses were performed to identify the prognostic factors.ResultsA total of 76 patients were included in the analysis. The median OS was 16 months and the rates of 2-year FFLP, PFS, and OS were 61%, 25%, and 33%, respectively. Among the evaluable patients, the first site of failure was the locoregional area in 16 patients, distant metastasis in 27, and both sites in 8. On univariate analysis, disease-free interval (p = 0.012) and concurrent chemotherapy (p = 0.040) were found as significant prognostic factors for OS. One patient with CCRT developed a grade 3 hematologic toxicity, and two patients experienced late grade 3 toxicities including duodenal ulcer bleeding and obstruction.ConclusionsRT for recurrent EHBDC showed favorable survival and local control with limited treatment-related toxicities. Considering that the most common pattern of failure was distant metastasis, further studies on the optimal scheme of chemotherapy and RT are warranted.

The outcomes of cutaneous head and neck angiosarcoma with different treatment modalities and correlation with inflammatory markers.

e23527 Background: Head and neck angiosarcoma (HN-AS) is a distinct entity that commonly arises from the scalp of elderly Asian males. We strive to study the impact of different treatment modalities and explore correlation with blood inflammatory markers. Methods: A prospectively maintained database was queried for patients with biopsy-confirmed HN-AS treated in a single tertiary institution from 2000 to 2018. Results: Eight-eight patients were analyzed. Median age is 73.5 (IQR 66-81.2). Fifty-five (64%) were non-metastatic at diagnosis, seventy-four (84.1%) arose from the scalp and 70.5% were males. Of the 55 non-metastatic patients, 21 received curative surgery and 7 patients received adjuvant radiotherapy. Patients who had curative surgery had smaller tumors (p < 0.001). Local relapses were 57.1% vs 35.7% without and with radiotherapy (p = 0.34). Five patients were still alive at time of analysis but only 1 with a follow up of more than 5 years. In this group, 2-year and 5-year locoregional progression free survival (PFS) were 56.0% and 26.1%, distant PFS were 73.7% and 41.4%, OS were 48.6% and 17.7%. In the group that was metastatic at presentation (n = 31), 17 patients received palliative chemotherapy with 7 patients documented as partial response. 17 patients received palliative radiotherapy with largely good symptomatic relief. Six patients received photodynamic therapy: with 1 documented abscopal response. The median survival is 6.9 months. Overall, 64 patients received palliative chemotherapy and 42 received palliative radiotherapy (in the metastatic or inoperable setting). The most common chemotherapy regimen was single agent paclitaxel (56.3%). In the first line setting, 66.7% experienced at least a partial response to chemotherapy. Comparing the 3 different treatment groups (metastastic vs curative surgery vs non-metastatic/no curative surgery), patient with curative surgery had the best OS (p = 0.007) but worse PFS compared to non-metastatic but no curative surgery patients (p = 0.03). Using full blood count at diagnosis, hazard ratio for neutrophil lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) were 1.02 (p = 0.06) and 0.80 (p = 0.02) respectively for OS. In multivariate analysis, age, stage and LMR were the only 3 significant predictors for OS. Conclusions: Cutaneous HN-AS is an aggressive disease. Although patients who had curative surgery had better overall survival which could be confounded by smaller tumours, and they also had earlier documented relapses possibly due to closer surveillance or tumor growth promotion from post-surgical inflammatory response. The value of adjuvant radiotherapy is unknown. Palliative radiotherapy is useful, and a more hypo-fractionated approach should be favored. Palliative single-agent paclitaxel is effective although overall survival remains grave. Blood inflammatory indicators correlate with survival.

Distribution of Peripheral Blood Cells in Esophageal Cancer Patients During Concurrent Chemoradiotherapy Predicts Long-Term Locoregional Progression Hazard After Treatment (GASTO1072).

PurposePredicting the response to chemoradiotherapy is critical for the optimal management of esophageal cancer; however, it remains an unmet clinical need. This study aimed to evaluate the predictive potential of peri-treatment peripheral blood cells (PBC) in disease progression hazard in esophageal cancer following chemoradiotherapy.Patients and MethodsA total of 87 patients with primary esophageal squamous cell carcinoma were subjected to definitive concurrent chemoradiotherapy in a Phase II trial. PBC parameters (hemoglobin, neutrophils, platelets, lymphocytes, and monocytes) were collected at seven time points throughout the course of radiotherapy. The potential of peri-treatment PBC parameters to predict the 3-year cumulative hazard of tumor progression was evaluated.ResultsPatients with disease progression displayed distinct distribution patterns of peri-treatment PBC compared to that in patients without disease progression. Greater prediction capabilities for risk of locoregional disease progression were found in PBC collected after the start of radiotherapy compared to those in their pretreatment counterparts, and in individual parameters rather than cell-to-cell ratios. The most predictive PBC parameters were integrated by summation and designated as a PBC score (PBCS), which further augmented their predictive power. Patients classified according to their PBCS (high vs medium v. low) had significantly different 3-year cumulative hazards of locoregional progression (58% vs 29% vs 7%, P = 0.0017). Multivariate analysis confirmed that high PBCS (HR, 12.2; 95% CI, 2.0–76.3; P = 0.007) and medium (HR, 5.8; 95% CI 1.2–27.7; P = 0.028) were independent indicators of locoregional progression.ConclusionSystematic analysis of PBC distribution in esophageal cancer patients undergoing definitive chemoradiotherapy could help predict long-term locoregional progression hazard after treatment.

Dose-escalated radiotherapy with PET/CT based treatment planning in combination with induction and concurrent chemotherapy in locally advanced (uT3/T4) squamous cell cancer of the esophagus: mature results of a phase I/II trial

BackgroundThis prospective phase I/II trial assessed feasibility and efficacy of dose-escalated definitive chemoradiation after induction chemotherapy in locally advanced esophageal cancer. Primary study endpoint was loco-regional progression-free survival at 1 year.MethodsEligible patients received 2 cycles of induction chemotherapy with irinotecan, folinic acid and 5-fluorouracil weekly and cisplatin every 2 weeks (weeks 1–6, 8–13) followed by concurrent chemoradiation with cisplatin and irinotecan (weeks 14, 15, 17, 18, 20). Radiotherapy dose escalation was performed in three steps (60 Gy, 66 Gy, 72 Gy) using conventional fractionation, planning target volumes were delineated with the aid of 18F-FDG-PET/CT scans. During follow-up, endoscopic examinations were performed at regular intervals.ResultsBetween 09/2006 and 02/2010, 17 patients were enrolled (male/female:13/4, median age: 59 [range 48–66] years, stage uT3N0/T3N1/T4N1: 4/12/1). One patient progressed during induction chemotherapy and underwent surgery. Of 16 patients treated with definitive chemoradiotherapy, 9 (56%) achieved complete response after completion of chemoradiation. One-, 2-, 3- and 5-year overall survival rates (OS) were 77% [95%CI: 59–100], 53% [34–83], 41% [23–73], and 29% [14–61], respectively. Loco-regional progression-free survival at 1, 3, and 5 years was 59% [40–88], 35% [19–67], and 29% [14–61], corresponding cumulative incidences of loco-regional progressions were 18% [4–39%], 35% [14–58%], and 41% [17–64%]. No treatment related deaths occurred. Grade 3 toxicities during induction therapy were: neutropenia (41%), diarrhoea (41%), during combined treatment: neutropenia (62%) and thrombocytopenia (25%).ConclusionsDose-escalated radiotherapy and concurrent cisplatin/irinotecan after cisplatin/irinotecan/5FU induction chemotherapy was tolerable. The hypothesized phase II one-year loco-regional progression free survival rate of 74% was not achieved. Long-term survival compares well with other studies on definitive radiotherapy using irinotecan and cisplatin but is not better than recent trials using conventionally fractionated radiotherapy ad 50 Gy with concurrent paclitaxel or 5FU and platinum compound.Trial registration The present trial was registered as a phase I/II trial at the EudraCT database: Nr. 2005-006097-10 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-006097-10/DE) and authorized to proceed on 2006-09-25.

Treatment of genitourinary carcinoma in dogs using nonsteroidal anti-inflammatory drugs, mitoxantrone, and radiation therapy: A retrospective study.

BackgroundLocoregional tumor control and prolonged survival for dogs with genitourinary carcinoma (CGUC) reportedly are achievable using treatment with radiotherapy (RT) with or without adjunctive chemotherapy and nonsteroidal anti‐inflammatory drugs (NSAIDs).ObjectivesTo characterize event‐free and overall survival after treatment of CGUC using NSAIDs, mitoxantrone (MTX), and a standardized RT protocol (57 Gy in 20 fractions).AnimalsFifty‐one client‐owned dogs treated between 2008 and 2017.MethodsDogs were retrospectively categorized into treatment groups: (a) first‐line concurrent chemoradiotherapy (≥1 dose of MTX started within 1 month of RT); (b) first‐line chemotherapy (MTX administered for >1 month before RT without tumor progression); (c) RT as a salvage procedure (MTX, surgery or both with subsequent locoregional tumor progression before RT). Treatment‐induced toxicoses, event‐free survival (EFS), and overall survival times (OSTs) were recorded. The influence of demographics, staging, and treatment‐related factors on survival was assessed using Cox proportional hazards modeling.ResultsMedian EFS and OST for all dogs were 260 and 510 days with no significant differences among groups 1 (n = 39), 2 (n = 4), and 3 (n = 8). Both EFS and OST were shorter in dogs with moderate to severe clinical signs (P < .001 and P < .001, respectively); OST was shorter in dogs with prostatic involvement (P = .02). Permanent urinary incontinence developed in 16 dogs (31%) at a median of 70 days postirradiation; other toxicoses were mild and self‐limiting.Conclusions and Clinical ImportanceMild clinical signs and lack of prostate involvement were associated with favorable prognosis for survival. Client education regarding the risk of urinary incontinence is warranted.

Phase I trial of the MEK inhibitor selumetinib in combination with thoracic radiotherapy in non-small cell lung cancer

BackgroundThe RAS/RAF/MEK/ERK signalling pathway has a pivotal role in cancer proliferation and modulating treatment response. Selumetinib inhibits MEK and enhances effects of radiotherapy in preclinical studies. Patients and methodsSingle-arm, single-centre, open-label phase I trial. Patients with stage III NSCLC unsuitable for concurrent chemo-radiotherapy, or stage IV with dominant thoracic symptoms, were recruited to a dose-finding stage (Fibonacci 3 + 3 design; maximum number = 18) then an expanded cohort (n = 15). Oral selumetinib was administered twice daily (starting dose 50 mg) commencing 7 days prior to thoracic radiotherapy, then with radiotherapy (6–6.5 weeks; 60–66 Gy/30–33 fractions). The primary objective was to determine the recommended phase II dose (RP2D) of selumetinib in combination with thoracic radiotherapy. Results21 patients were enrolled (06/2010–02/2015). Median age: 62y (range 50–73). M:F ratio 12(57%):9(43%). ECOG PS 0:1, 7(33%):14(67%). Stage III 16(76%); IV 5(24%). Median GTV 64 cm3 (range 1–224 cm3). 15 patients comprised the expanded cohort at starting dose. All 21 patients completed thoracic radiotherapy as planned and received induction chemotherapy. 13 (62%) patients received the full dose of selumetinib.In the starting cohort no enhanced radiotherapy-related toxicity was seen. Two patients had dose-limiting toxicity (1x grade 3 diarrhoea/fatigue and 1x pulmonary embolism). Commonest grade 3–4 adverse events: lymphopaenia (19/21 patients) and hypertension (7/21 patients). One patient developed grade 3 oesophagitis. No patients developed grade ≥3 radiation pneumonitis. Two patients were alive at the time of analysis (24 and 26 months follow-up, respectively). Main cause of first disease progression: distant metastases ± locoregional progression (12/21 [57.1%] patients). Six patients had confirmed/suspected pneumocystis jiroveci pneumonia. ConclusionWe report poor outcome and severe lymphopenia in most patients treated with thoracic radiotherapy and selumetinib at RP2D in combination, contributing to confirmed/clinically suspected pneumocystis jiroveci pneumonia. These results suggest that this combination should not be pursued in a phase II trial.ClinicalTrials.gov reference: NCT01146756.

Abstract PS10-34: Clinical outcomes in de novo metastatic HER2-positive inflammatory breast cancer

Abstract Background: Advances in HER2-directed therapy have significantly improved survival in HER2+ metastatic breast cancer. Approximately 30% of de novo metastatic inflammatory breast cancer (mIBC) is HER2+, though there has been limited IBC representation in clinical trials evaluating the role of HER2-directed agents as first-line metastatic therapy. Elevated rates of locoregional progression or recurrence (LRPR) with systemic therapy alone also raise the question of whether trimodality therapy (TMT) may improve outcomes in IBC patients (pts) with limited metastatic disease, particularly in the setting of increasingly effective anti-HER2 therapy. Methods: Pts diagnosed with de novo HER2+ mIBC were identified from an IRB-approved IBC registry at Dana-Farber Cancer Institute. Clinical, pathology and treatment data were manually abstracted by chart review. Progression-free survival (PFS) was defined as time from IBC diagnosis to LRPR, distant progression/relapse or death (in the absence of event, censored at date of last follow-up). Overall survival (OS) was defined as time from IBC diagnosis to death from any cause or censored at date last known alive. For pts who underwent surgery of the primary tumor, pathologic complete response (pCR) was defined as no residual invasive carcinoma in the breast and axilla and survival was estimated from date of surgery. Median PFS and OS were estimated by Kaplan-Meier method; cumulative incidence of CNS metastasis and LRPR were estimated with death as competing risk. Results: 78 pts diagnosed between 1998-2019 with de novo HER2+ mIBC (41 hormone receptor (HR)-positive; 37 HR-negative) were identified. Median age at diagnosis was 53 years (yr; range: 24-91). Sites of metastatic disease at presentation included bone only (n=12), lymph node/contralateral chest wall only (n=17), bone and lymph node (n=5), visceral (n=40) and CNS with extracranial disease (n=4). As initial HER2-directed therapy, 37 pts received trastuzumab (H), 40 H plus pertuzumab and 1 T-DM1. At a median follow-up of 2.7 yr in the overall cohort, median PFS was 1.0 yr (IQR: 0.5-2.8 yr; 60 events) and median OS was 4.6 yr (IQR: 2.9-8.7 yr; 39 deaths). 34 pts had CNS metastasis with a cumulative incidence of 20% and 28% at 1 and 2 yr, respectively. LRPR developed in 26 pts, of which 16 occurred within 12 months (mo) of diagnosis. Cumulative incidence of LRPR at 1 and 2 yr was 21% and 29%, respectively. In 41 pts (53%), mastectomy was performed after receipt of systemic therapy. Median time from IBC diagnosis to surgery was 7.5 mo (IQR: 6.0-9.9 mo). Radiation was administered in 33 pts, 3 pre- and 30 post-mastectomy. Median OS from surgery was 5.2 yr (IQR: 3.1-8.4 yr). 9/41 pts (22%) achieved pCR; all pCR pts were alive at 1.3-8.9 yr since surgery. To investigate the value of therapy for locoregional control, a landmark analysis was performed in the subset of pts alive and LRPR free at 12 mo from diagnosis (n=56). 27 had surgery within 12 mo from diagnosis and 29 did not. LRPR occurred in 10/56; 9 were among pts who did not undergo surgery. Cumulative LRPR incidence at 1 and 2 yr since the 12 mo landmark was 21% and 29%, respectively, in pts who did not undergo surgery, and 0% at both time points in pts who had surgery (1 LRPR at 8 yr). Conclusion: Long-term outcomes in de novo HER2+ mIBC are overall similar to those reported in metastatic HER2+ non-IBC. More than half of pts underwent systemic and local therapy with good locoregional control and prolonged survival, suggesting a potential role for aggressive local therapy in this mIBC subset with favorable prognosis and effective systemic therapy. The high incidence of early CNS involvement in de novo HER2+ mIBC prompted us to explore this group in detail (Warren SABCS 2020 abstract). Larger studies are needed to better understand the effectiveness of TMT in HER2+ mIBC, highlighting the importance of collaborative research efforts in this rare subset. Citation Format: Ana C. Garrido-Castro, Samuel M. Niman, Marie Claire Remolano, Jennifer M. Rosenbluth, Caroline Block, Laura E. Warren, Jennifer Bellon, Beth T. Harrison, Faina Nakhlis, Meredith Regan, Beth Overmoyer. Clinical outcomes in de novo metastatic HER2-positive inflammatory breast cancer [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 PS10-34.

Radiotherapy for Primary Tracheal Carcinoma: Experience at a Single Institution

Background:There is limited understanding of tracheal carcinoma (TC) because of its rarity. We examined the efficacy of radiotherapy (RT) for patients with primary TC.Methods:We analyzed the records of 32 patients with primary TC who received RT at our center between November 1996 and December 2016.Results:Thirteen patients received adjuvant RT and 18 received definitive RT. Eight patients achieved complete remission (CR) after definitive RT. Among all patients, the 5-year overall survival (OS) rate was 46.9% and the locoregional progression free survival (LRPFS) rate was 68.1%. Univariate analysis indicated the 5-year OS was better in those with adenoid cystic adenocarcinoma than squamous cell carcinoma (P = 0.001); the 5-year LRPFS was better in patients who received surgical resection than those who did not (92.9% vs 46.4%, P = 0.013) and in patients who received postoperative RT than in those who received definitive RT (91.7% vs 50.1%, P = 0.038). A sub-group univariate analysis indicated the 5-year PFS was better for those who received at least 68 Gy of radiation (44.4% vs 13.0%, P = 0.044). Patients who achieved CR had a better 5-year PFS than those who did not (57.1% vs 10%, P = 0.006). No patients had a toxicity of grade 3 or more.Conclusions:Adjuvant and definitive RT are safe and effective treatments for TC. Patients who received dosages of 68 Gy or more and who had complete tumor regression following definitive RT seemed to have better long-term survival.

Chemoradiotherapy for patients with locally advanced or unresectable extra-hepatic biliary cancer.

Although surgical resection is the preferred curative-intent treatment option for patients with non-metastatic, extra-hepatic biliary cancer (EBC), radiotherapy (RT) or chemoradiotherapy (CRT) may be utilized in select cases when surgical resection is not feasible. The purpose of this study is to report the efficacy and adverse events (AEs) associated with CRT for patients with locally advanced and unresectable EBC. This was a retrospective cohort study of patients with EBC, including extra-hepatic cholangiocarcinoma or gallbladder cancer, deemed inoperable who received RT between 1998 and 2018. The median RT dose was 50.4 Gy in 28 fractions and 94% received concurrent 5-fluorouracil. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) from the start of RT. The cumulative incidence of local progression (LP), locoregional progression (LRP), and distant metastasis (DM) were reported with death as a competing risk. Cox proportional hazards regression models were used to assess for correlation between patient and treatment characteristics and outcomes. Forty-eight patients were included for analysis. The median OS was 12.0 months [95% confidence interval (CI): 2.3-73.2 months]. The 2-, 3-, and 5-year OS were 33% (95% CI: 22-50%), 20% (95% CI: 11-36%), and 7% (95% CI: 2-20%), respectively. The 2-year PFS, LP, LRP, and DM were 21% (95% CI: 12-36%), 27% (95% CI: 17-44%), 31% (95% CI: 20-48%), and 33% (95% CI: 22-50%), respectively. On univariate analysis, biologically effective dose (BED) >59.5 Gy10 was associated with improved OS [hazard ratio (HR): 0.40, 95% CI: 0.18-0.92, P=0.03] and PFS (HR: 0.37, 95% CI: 0.16-0.84, P=0.02) and primary tumor size (per 1 cm increase) was associated with worsened PFS (HR: 1.29, 95% CI: 1.02-1.63, P=0.04). BED >59.5 Gy10 remained associated with PFS on multivariate analysis (HR: 0.34, 95% CI: 0.15-0.78, P=0.01). Treatment-related grade 3+ acute and late gastrointestinal AEs occurred in 13% and 17% of patients, respectively. RT is associated with 3- and 5-year survival in a subset of patients with unresectable EBC. Further exploration of the role of RT as part of a multi-modality curative treatment strategy is warranted.

Sequential Hypofractionated Radiotherapy can Offer Similar Disease Control and Survival of Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer?

Concurrent conventional fractionated chemoradiation (ccCRT) is the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC) when compared with convectional fractionated radiation therapy (cfRT) after chemotherapy. The main benefit of ccCRT is associated to disease locoregional control. Sequential Hypofractionated Radiation therapy (s-HypoRT) is a treatment option for these patients. We compared the outcomes of the ccCRT with sequential treatment cfRT and s-HypoRT. It was a retrospective analysis of all inoperable stage III LA-NSCLC submitted to radical radiotherapy (RT) in a single institution from January 2013 to October 2018. Patients submitted to ccCRT and cfRT received 60Gy in 30 fractions. The patients submitted to s-HypoRt received 55Gy in 20 fractions. All patients were treated with conformal RT or IMRT. All chemotherapy schedule was platinum doublet based. Patients submitted All Patients were (re)staged according to the AJCC 8a ed. The criteria for disease progression was based on RECIST v1.1 and the toxicity criteria used was the CTCAE.v4. Survival analysis was evaluated by Kaplan–Meier method and log-rank test. Multivariate models were tested including all covariates with p values < .20 in the univariate analysis. It was recorded the medical charts and treatment planning of 140 patients. The median age was 63 years (range, 25–83). Most were male (61%) and had ECOG Performance Status 1 (72%). The stage distribution was IIIA 32%, IIIB 51% and IIIC 17%. The patient populations were divided in 3 groups: 52 patients (37%) were submitted to cc-CRT, 38 patients (27%) was submitted to sequential cfRT (cfRTSeq) and 50 patients (36%) received s-HypoRT. With the median follow up of 16 months, the median Overall Survival (OS) for the entire population was 23 months and there was no difference in OS between the 3 groups (p = 0,686). Large tumor volume (p = 0,039) and use of IMRT (p = 0,031), was associated with OS on univariate analysis. The 2-years Locoregional Progression Free Survival (LPFS) 62.9% for ccCRT, x 60.0% for s-HypoRT and 41.0% for cfRTSeq (p = 0.031). On multivariate analysis the cfRTSeq (HR 2,11, IC 1,06—4,19) was associated with worse LRPFS. The treatment was well tolerated for all groups, and the rates of grade ≥ 3 acute esophagitis of 1.9% for ccCRT and 4.0% for s-HypoRT (p = ns). Only one case of grade 3 fatigue was evidenced in the cfRTSeq and one case of grade 3 pneumonitis was evidenced in the ccCRT and cfRT group. Our data demonstrated that s-HypoRT results in similar LRPFS when compared with the standard ccCRT. There was no difference in OS. S-HypoRT is a safe and fast treatment strategy for patients not suitable for ccCRT and can be considered a better option than cfRTSeq.

Prediction of post-radiotherapy locoregional progression in HPV-associated oropharyngeal squamous cell carcinoma using machine-learning analysis of baseline PET/CT radiomics

Locoregional failure remains a therapeutic challenge in oropharyngeal squamous cell carcinoma (OPSCC). We aimed to devise novel objective imaging biomarkers for prediction of locoregional progression in HPV-associated OPSCC. Following manual lesion delineation, 1037 PET and 1037 CT radiomic features were extracted from each primary tumor and metastatic cervical lymph node on baseline PET/CT scans. Applying random forest machine-learning algorithms, we generated radiomic models for censoring-aware locoregional progression prognostication (evaluated by Harrell's C-index) and risk stratification (evaluated in Kaplan-Meier analysis). A total of 190 patients were included; an optimized model yielded a median (interquartile range) C-index of 0.76 (0.66-0.81; p = 0.01) in prognostication of locoregional progression, using combined PET/CT radiomic features from primary tumors. Radiomics-based risk stratification reliably identified patients at risk for locoregional progression within 2-, 3-, 4-, and 5-year follow-up intervals, with log-rank p-values of p = 0.003, p = 0.001, p = 0.02, p = 0.006 in Kaplan-Meier analysis, respectively. Our results suggest PET/CT radiomic biomarkers can predict post-radiotherapy locoregional progression in HPV-associated OPSCC. Pending validation in large, independent cohorts, such objective biomarkers may improve patient selection for treatment de-intensification trials in this prognostically favorable OPSCC entity, and eventually facilitate personalized therapy.

Locoregional control, progression-free survival and morbidity rates in N3 head and neck cancer patients with low primary tumour burden: A 301-patient study.

In patients with N3 head and neck squamous cell carcinoma (HNSCC), N3 disease is associated with high regional relapse and metastatic risks. Patients with resectable N3 disease have better prognosis although their metastatic risk may be similar as in patients with unresectable disease. Neoadjuvant chemotherapy has been associated with lower metastatic rates, but N3 patients may die of rapid locoregional progression. We assessed outcomes with the three modalities in patients with low primary burden to better assess the specific prognosis of N3 disease. This retrospective multicentric study included T0-2 N3 HNSCC patients. Outcomes and morbidity in upfront neck dissection (uND) vs non-surgical groups were analysed and oncological outcomes and morbidity compared between patients undergoing chemoradiation or neoadjuvant chemotherapy in patients with initially unresectable N3 nodes. Of 301 patients, 142 (47%) underwent uND, 68 (23%) neoadjuvant chemotherapy and 91 (30%) chemoradiation. The 24- and 60-month incidence of locoregional relapse was 23.2% [18.3%; 28.4%] and 27.4% [21.8%; 33.3%]; it was lower in patients undergoing uND (P=.006). In patients with non-surgical treatments, success rates were 57.8% [49.4%; 66.3%] after chemoradiation and 38.1% [29.6%; 46.7%] after neoadjuvant chemotherapy (P=.001). Overall morbidity was more frequent in patients undergoing uND (68.8%) (P<.001). uND improved locoregional control but increased morbidity and showed no survival benefit. Success rates were better after chemoradiation versus neoadjuvant chemotherapy. Neoadjuvant chemotherapy did not reduce metastatic rates but non-responders to chemoradiation had poor PFS and survival rate, suggesting that predictive criteria are warranted.

Progresión locorregional de carcinoma mioepitelial de la mama postratamiento quimiorradioterápico. Resección y cobertura con colgajo de avance

Myoepithelial carcinoma of the breast is an uncommon tumour with few cases reported in the literature. Consequently, it is a diagnostic and therapeutic challenge. Treatment includes the design of local flaps. We present a case of myoepithelial carcinoma of the breast with locoregional progression after chemotherapy and radiotherapy. We also provide a review of the literature, allowing us to establish a definitive diagnosis and optimal oncological and surgical treatment with reconstruction of this tumour.

A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108).

LBA2 Background: About 6% of newly diagnosed breast cancer patients present with Stage IV disease and an intact primary tumor (IPT). Locoregional treatment (LRT) for the IPT is hypothesized to improve survival based on retrospective analyses, but randomized trials have provided conflicting data. We now report the results of E2108, a Phase 3 trial that examined the worth of LRT for the IPT following initial systemic therapy. Methods: Stage IV patients with IPT were registered, treated with optimal systemic therapy (OST) based on patient and tumor characteristics; those who did not progress during 4-8 months of OST were randomized to LRT for the IPT, or no LRT. The primary endpoint was overall survival (OS), with locoregional disease control as a secondary endpoint. Stratified log rank test and Cox proportional hazard model were used to compare OS between treatment groups. Cumulative incidence of locoregional recurrence/progression was estimated and Gray test was used for treatment group comparisons. The trial was designed to detect an improvement in 3 year OS rate from 30% with OST alone to 49.3% for OST+LRT (power 95%, 1-sided alpha 0.05) with full information expected after 152 deaths; the data monitoring committee recommended data release after 80% of full information. Results: 390 patients were enrolled between 2/8/11 and 7/23/15, and received OST. Of these, 256 eligible patients were randomized to either continued OST alone (N = 131) or OST+LRT (N = 125).There were 121 deaths and 43 locoregional progression events after a median follow up 59 months (range: 0-91). There was no significant difference in OS (3-year OS rate 68.4% in OST+LRT vs. 67.9% OST alone arm, stratified log-rank p = 0.63, HR = 1.09, 90% CI: 0.80, 1.49) or in progression-free survival (p = 0.40). The locoregional recurrence/progression was significantly higher in the OST alone arm (3-year rate 25.6% vs 10.2%, Gray test p = 0.003). Health-related quality of life (HRQOL) measured by FACT-B Trial Outcome Index was significantly worse in the OST+LRT arm than OST alone arm at 18 months post randomization (60% completion, Wilcoxon rank sum test p = 0.01), but no difference was observed at time points 6 months (74% completion) or 30 months (56% completion). Conclusions: Early local therapy does not improve survival in patients with de novo metastatic breast cancer and an IPT. Although there was a 2.5-fold higher risk of local disease progression without LRT, LRT of the IPT did not lead to improved HRQOL. Clinical trial information: NCT01242800 .

A phase II randomized trial of RAdium-223 dichloride and SABR Versus SABR for oligomEtastatic prostate caNcerS (RAVENS)

BackgroundMetastasis directed therapy (MDT) for patients with oligometastatic disease is associated with improvements in progression free survival (PFS) and overall survival (OS) compared to systemic therapy alone. Additionally, within a prostate-cancer-specific cohort, MDT is able to forestall initiation of androgen deprivation therapy (ADT) in men with hormone-sensitive, oligometastatic prostate cancer (HSOPCa) compared to observation. While MDT appears to be safe and effective in HSOPCa, a large percentage of men will eventually have disease recurrence. Patterns of failure in HSOPCa demonstrate patients tend to have recurrence in the bone following MDT, raising the question of sub-clinically-apparent osseous disease. Radium-223 dichloride is a radiopharmaceutical with structural similarity to calcium, allowing it to be taken up by bone where it emits alpha particles, and therefore might have utility in the treatment of micrometastatic osseous disease. Therefore, the primary goal of the phase II RAVENS trial is to evaluate the efficacy of MDT + radium-223 dichloride in prolonging progression free survival in men with HSOPCa.MethodsPatients with HSOPCa and 3 or less metastases with at least 1 bone metastasis will be randomized 1:1 to stereotactic ablative radiation (SABR, also known as stereotactic body radiation therapy (SBRT)) alone vs SABR + radium-223 dichloride with a minimization algorithm to balance assignment by institution, primary intervention, prior hormonal therapy, and PSA doubling time. SABR is delivered in one to five fractions and patients in the SABR + radium-223 dichloride arm will receive six infusions of radium-223 dichloride at four-week intervals. The primary end point is progression free survival. The secondary clinical endpoints include toxicity and quality of life assessments, local control at 12 months, locoregional progression, time to distant progression, time to new metastasis, and duration of response.DiscussionThe RAVENS trial will be the first described phase II, non-blinded, randomized study to compare SABR +/− radium-223 dichloride in patients with HSOPCa and 3 or less metastases with at least one bone metastasis. The primary hypothesis is that SABR + radium-223 dichloride will increase median progression-free survival from 10 months in the SABR arm to 20 months in the SABR + radium-223 dichloride arm.Trial registrationsClinicaltrials.gov. Identifier: NCT04037358. Date of Registration: July 30, 2019. Date of First Participant Enrolled: August 9, 2019. Date of Last Approved Amendment: October 16, 2019. Protocol Version: Version 5.

A phase II randomized trial of RAdium-223 dichloride and SABR versus SABR for oligomEtastatic prostate caNcerS (RAVENS).

TPS5586 Background: Metastasis directed therapy (MDT) is able to prolong progression free survival (PFS) and forestall initiation of androgen deprivation therapy (ADT) in men with hormone-sensitive, oligometastatic prostate cancer (HSOPCa) compared to observation. While MDT appears to be effective in HSOPCa, a large percentage of men will have disease recurrence. Patterns of failure demonstrate patients tend to recur in the bone following MDT, raising the question of sub-clinically-apparent osseous disease. Radium-223 dichloride is a radiopharmaceutical with structural similarity to calcium, allowing it to be taken up by bone where it emits alpha particles, and therefore might have utility in the treatment of micrometastatic osseous disease. Therefore, the primary goal of the phase II RAVENS trial is to evaluate the efficacy of Stereotactic ablative radiation (SABR) + radium-223 dichloride in prolonging PFS in men with HSOPCa. Methods: Patients with HSOPCa and 3 or less metastases with at least 1 bone metastasis (by conventional imaging) will be randomized 1:1 to SABR alone vs. SABR + radium-223 dichloride. Eligibility criteria include PSA doubling time of &lt; 15 months and ECOG performance status of &lt; 2. Patients cannot be on ADT and must have normal testosterone levels at the time of randomization. Patients randomized to the combination arm will receive six doses of Radium-223 dichloride at four week intervals. A sample size using a 1:1 randomization scheme of 30 patients per arm will provide 80% power to detect an increase of median PFS from 10 months to 20 months with type I error = 0.1, using a one-sided log-rank test. To account for 5% early drop out, we will randomize a total of 64 patients (32 per arm). The primary end point is PFS with a primary hypothesis that SABR + radium-223 dichloride will increase median PFS from 10 months in the SABR arm to 20 months in the SABR + radium-223 dichloride arm. Progression is a composite endpoint including PSA progression per Prostate Cancer Working Group 2 (PCWG2), symptomatic progression, radiologic progression per RECIST 1.1 criteria, initiation of ADT, or death due to any cause. Secondary clinical endpoints include toxicity and quality of life assessments, local control at 12 months, locoregional progression, time to distant progression, time to new metastasis, and duration of response. Biological correlates will be evaluated including changes in circulating tumor cells following therapy, deep sequencing of circulating tumor DNA, and T-cell repertoire profiling before and after therapy. Clinical trial information: NCT04037358 .

Concurrent cisplatin and dose escalation with intensity-modulated radiotherapy (IMRT) versus conventional radiotherapy for locally advanced head and neck squamous cell carcinomas (HNSCC): GORTEC 2004-01 randomized phase III trial

BackgroundConcurrent chemoradiotherapy (CRT) is the standard of care (SoC) in locally advanced (LA) head and neck squamous cell carcinomas (HNSCC). This trial was designed to test whether dose-escalated IMRT and cisplatin could improve locoregional control without increasing complications over 3D-radiotherapy. MethodsPatients were randomized between 70 Gy/35F in 7 weeks with 3D-RT (Arm A) versus 75 Gy/35F with IMRT (Arm B). Both arms received 50 Gy in 25 fractions followed by a sequential boost of 20 Gy/10F in Arm A and 25 Gy/10F to gross tumor volume in Arm B, as well as 3 cycles of cisplatin at 100 mg/m2 during RT. The primary endpoint was locoregional progression (LRP). Results188 patients were randomized: 85% oropharynx and 73% stage IVa. P16 status was documented for 137 oropharyngeal tumors with P16+ in 53 (39%) patients; and 90% were smokers. Median follow-up was 60.5 months. Xerostomia was markedly decreased in arm B (p < 0.0001). The 1-year grade ≥2 xerostomia (RTOG criteria) was 63% vs 23% and 3-year 45% vs 11% in arms A and B, respectively. Xerostomia LENT-SOMA scale was also reduced in arm B. Dose-escalated IMRT did not reduce LRP with an adjusted HR of 1.13 [95%CI = 0.64–1.98] (p = 0.68). Survival was not different (adjusted HR: 1.19 [95%CI = 0.78–1.81], p = 0.42). No interaction between p16 and treatment effect was found. ConclusionDose-escalated IMRT did not improve LRC in LA-HNSCC patients treated with concomitant CRT over standard 3D-RT. This trial reinforces the evidence showing IMRT reduces xerostomia in LA-HNSCC treated with radiotherapy.Clinicaltrial.gov: NCT00158678.

Randomized controlled trial to identify the optimal radiotherapy scheme for palliative treatment of incurable head and neck squamous cell carcinoma

BackgroundNo randomized controlled trials (RCT) have yet identified the optimal palliative radiotherapy scheme in patients with incurable head and neck squamous cell carcinoma (HNSCC). We conducted RCT to compare two radiation schemes in terms of efficacy, toxicity and quality-of-life (QoL). Materials and methodsPatients with locally-advanced HNSCC who were ineligible for radical treatment and those with limited metastatic disease were randomly assigned in 1:1 ratio to arm 1 (36 Gy in 6 fractions, twice a week) or arm 2 (50 Gy in 16 fractions, four times a week). ResultsThe trial was discontinued early because of slow accrual (34 patients enrolled). Objective response rates were 38.9% and 57.1% for arm 1 and 2 respectively (p = 0.476). The median time to loco-regional progression was not reached. The loco-regional control rates at 1 year was 57.4% and 69.3% in arm 1 and 2 (p = 0.450, HR = 0.56, 95%CI 0.12–2.58). One-year overall survival was 33.3% and 57.1%, with medians of 35.4 and 59.5 weeks, respectively (p = 0.215, HR = 0.55, 95%CI 0.21–1.43). Acute grade ≥3 toxicity was lower in arm 1 (16.7% versus 57.1%, p = 0.027), with the largest difference in grade 3 mucositis (5.6% versus 42.9%, p = 0.027). However, no significant deterioration in any of the patient-reported QoL-scales was found. ConclusionNo solid conclusion could be made on this incomplete study which is closed early. Long-course radiotherapy did not show significantly better oncologic outcomes, but was associated with more acute grade 3 mucositis. No meaningful differences in QoL-scores were found. Therefore, the shorter schedule might be carefully advocated. However, this recommendation should be interpreted with great caution because of the inadequate statistical power.

MP70-07 TRANSPERINEAL FOCAL CRYOABLATION AS A TREATMENT FOR CLINICALLY SIGNIFICANT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy II (MP70)1 Apr 2020MP70-07 TRANSPERINEAL FOCAL CRYOABLATION AS A TREATMENT FOR CLINICALLY SIGNIFICANT PROSTATE CANCER Mark Kelly* and MD Jonatan Torrez Mark Kelly*Mark Kelly* More articles by this author and Jonatan TorrezJonatan Torrez More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000950.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate multiparametric MRI (mpMRI) with Index Lesion identification has led to questioning the need for whole gland therapies for carefully selected men harboring well-defined clinically significant malignant lesions. This investigation sought to determine the safety and efficacy of targeted focal ablative therapy in a community based urological practice. Our goal was to test the image-guided paradigm and to determine whether targeted biopsies were sufficient in assessing prostate cancer risk and whether truly focal target ablative therapy offered our patients a safe and effective alternative to whole gland therapy. We present our experience with our first 35 patients, diagnosed with clinically significant prostate cancer (csPC) managed with transperineal Focal Cryoablation (FC). METHODS: Subject patients were referred for PC detection due to elevated serum PSA. All patients underwent a mpMRI prior to transperineal biopsy. Men with PIRAD 3, 4 and 5 targets underwent both target and template transperineal fusion biopsy. Men diagnosed with Grade Groups (GG) 2, 3, and 4 index lesions were offered focal ablative transperineal cryoablation. Our follow up protocol called for post-ablation clinical evaluation, serial PSA determinations, post-ablation mpMRI and confirmatory biopsy (cBx). All patients were queried with pre and post-ablation SHIM and IPSS scoring. RESULTS: Patients were assessed on an Intent to Treat basis. Of the original 35 patients, 33/35 (94%) underwent post-ablation mpMRI. 19/35 (54%) have undergone post-ablative confirmatory biopsy.With mean follow up of 24 months, 29/33 men (88%) had post-ablation PIRAD ≤ 2 Scores. 14/19 (74%) had no cancer on cBx. 3/5 (60%) of positive post-ablation cBxs were GG 1. 2/5 (40%) of cBxs were GG 2. 4/33 (12%) of men undergoing follow up mpMRI developed new PIRAD 3 lesions (2 patients) or 4 lesions (2 patients). Zero new PIRAD 5 lesions were detected. No men had observable PSA elevations beyond baseline PSA at diagnosis. No men developed locoregional or systemic progression. 32/35 men (91%) adhered to follow up serial PSA testing.With a mean followup of 24 months, 28/32 (88%) of men had a sustained low serum PSA, with an average value of 1.8 ng/mL. No new or worsening erectile dysfunction or urinary incontinence occurred. CONCLUSIONS: Focal Cryoablation is a promising alternative to Whole Gland Therapy for proven focal significant lesions.Strict attention to disease staging and careful follow-up is essential to an effective Focal Ablative program. Source of Funding: Chan Soon-Shiong Nanthealth Foundation. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1057-e1057 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mark Kelly* More articles by this author Jonatan Torrez More articles by this author Expand All Advertisement PDF downloadLoading ...

Last-line local treatment with the Quad Shot regimen for previously irradiated head and neck cancers

Patients with prior irradiated head and neck cancer (HNC) who are ineligible for definitive retreatment have limited local palliative options. We report the largest series of the use of the Quad Shot (QS) regimen as a last-line local palliative therapy. We identified 166 patients with prior HN radiation therapy (RT) treated with QS regimen (3.7Gy twice daily over 2 consecutive days at 4weeks intervals per cycle, up to 4 cycles). Palliative response defined by symptom(s) relief or radiographic tumor reduction, locoregional progression free survival (LPFS), overall survival (OS) and radiation-related toxicity were assessed. Median age was 66years. Median follow-up for all patients was 6.0months and 9.7months for living patients. Overall palliative response rate was 66% and symptoms improved in 60% of all patients. Predictors of palliative response were>2year interval from prior RT and 3-4 QS cycles. Median LPFS was 5.1months with 1-year LPFS 17.7%, and median OS was 6.4months with 1-year OS 25.3%. On multivariate analysis, proton RT, KPS>70, presence of palliative response and 3-4 QS cycles were associated with improved LPFS and improved OS. The overall Grade 3 toxicity rate was 10.8% (n=18). No Grade 4-5 toxicities were observed. Palliative QS is an effective last-line local therapy with minimal toxicity in patients with previously irradiated HNC. The administration of 3-4 QS cycles predicts palliative response, improved PFS, and improved OS. KPS>70 and proton therapy are associated with survival improvements.