Locoregional Disease Control Research Articles

Importance of resection for locoregional disease control in Masaoka stage IVA thymic neoplasms.

It is unclear if a specific strategy for simultaneous treatment of primary thymic neoplasms and pleural metastases confers benefit for Masaoka stage IVA disease. We reviewed our experience with thymic neoplasms with concurrent pleural metastases to identify factors influencing outcomes. Records of patients who presented with stage IVA thymic neoplasms from 2000 to2018 were assessed. Multivariate Cox proportional hazards analyses were completed to determine predictors of progression-free and overall survival. Forty-eight patients were identified, including 34 (71%) who underwent surgery. Median overall and progression-free survival were 123 and 21 months, respectively. The extent of resection varied, and was most commonly thymectomy plus partial pleurectomy (22, 65%). Median progression-free survival for patients who underwent surgical resection versus those who had not was 24 versus 12 months (P = .018). Following surgical resection, mediastinal recurrence was uncommon (2, 6%, vs 7, 50% nonoperatively). Five-year survival rates in these groups were suggestive of possible benefit to surgery (87% vs 68%). Thymic neoplasms with pleural dissemination represents a treatment challenge. As part of a multidisciplinary approach, surgery appears to be associated with more favorable long-term results, although selection bias may account for some of the survival differences observed.

TO COMPARE THE EFFICACY OF CONCOMITANT BOOST RADIOTHERAPY AGAINST CONCURRENT CHEMORADIATION IN LOCALLY ADVANCED HEAD AND NECK CANCER (OROPHARYNX/LARYNX/ HYPOPHARYNX)

Background: Most head and neck cancers, indeed 95% or more, are squamous cell carcinomas (SCC) and variants thereof, originating from the epithelium of the mucosal lining of the upper aerodigestive tract (UADT), and adenocarcinomas from associated secretory glands.
 Methods: This prospective randomized study was conducted in the Department of Radiation Therapy & Oncology, Regional Cancer Centre, IGMC, Shimla and patients were enrolled for a period of one year, from July 2012 to July 2013.It included all the eligible, previously untreated patients of squamous cell carcinoma of Head and Neck with histologically confirmed diagnosis and no evidence of distant metastasis. The sites included were oro-pharynx, hypo-pharynx and larynx with stages III, IV A and IV B.
 Results: On first follow up, overall there was complete response at nodal site in 50 patients(69.4%) 26 in CRT arm (70.3%) and 24 in ART arm(68.6%), however the difference was not statistically significant (p=0.875).
 Conclusion: There was comparable locoregional disease control with the use of accelerated six fractions a week radiation therapy compared to concomitant chemoradiation with conventional fractionation.
 Keywords: Six fraction, Concomitant chemoradiation, Conventional fractionation.

Locoregional Control, Overall Survival, and Disease-Free Survival in Stage IIIA (N2) Non–Small-Cell Lung Cancer: Analysis of Resected and Unresected Patients

IntroductionThe standard of care for stage IIIA (N2) non–small-cell lung cancer (NSCLC) includes concurrent definitive chemoradiation (dCRT) followed by durvalumab, thus challenging the role of surgery in resectable patients. We assessed locoregional disease control and survival in patients with surgically resected and unresected stage IIIA (N2) NSCLC disease. Patients and MethodsWe conducted a retrospective analysis from prospectively collected databases at MD Anderson Cancer Center. Patients undergoing neoadjuvant chemotherapy and surgery or dCRT for clinical stage IIIA (N2) disease (2004-2014) were evaluated. Primary outcomes included locoregional disease control, disease-free survival (DFS), and overall survival (OS). Kaplan-Meier outcome analyses were performed. ResultsOf the 159 resected patients, the majority had lobectomy (82.4%), followed by pneumonectomy (11.9%) and sublobar resection (5.7%). The 30- and 90-day mortality rates were 0.6% and 1.3%, respectively. At median follow-up of 52.8 months, recurrence was 55.3%, with 44.0% having distant and 15.1% locoregional recurrence. At 5 years, OS was 50.8% and DFS was 33.1% Median OS was 61.2 months. A total of 366 patients underwent dCRT, with intensity-modulated radiation in 64.5%, proton therapy in 26.0%, and 3-dimensional conformal radiotherapy in 9.6%. The mean dose was 68.1 Gy. At median follow-up of 20.8 months, recurrence was 53.6%, with distant and locoregional recurrence of 40.7% and 30.3%, respectively. At 5 years, OS was 29.2% and DFS was 20.5%. Median OS was 27.5 months. ConclusionStage IIIA (N2) NSCLC continues to be a heterogeneous disease, and patients with surgically resected and unresected disease represent different risk populations. Ongoing immunotherapy trials may further redefine treatment algorithms in this complex patient population.

Neo-adjuvant chemotherapy followed by either continuous hyper-fractionated accelerated radiation therapy week-end less or conventional chemo-radiotherapy in locally advanced NSCLC-A randomised prospective single institute study.

Better locoregional control and increased overall survival by continuous hyper fractionated accelerated radiotherapy have been shown in unresectable nonsmall cell lung carcinoma (NSCLC). Dose escalation and neoadjuvant chemotherapy (NACT) along with continuous hyperfractionated accelerated radiotherapy week end-less (CHARTWEL) were also tried for improved survival. In this present study, we compared the results of NACT followed by CHARTWEL against NACT followed by conventional concurrent chemo-radiation therapy. The aim of this study is to compare the locoregional control and toxicities in NSCLC Stage IIIA and B in both arms. Randomized, prospective single-institutional study with a study population comprising all locally advanced unresectable NSCLC patients enrolled in 2014 at our institute. All enrolled patients were randomized into two arms-CHARTWEL and concomitant chemo-radiotherapy (CCRT), after three weeks of the fourth cycle of NACT. In CHARTWEL arm 30 patients received two-dimensional radiotherapy (RT) 58.5 Gy/39 fr/2.5 weeks while in CCRT arm 30 received 66 Gy/33 fr/6.5 weeks. Disease response was evaluated at 6 months and toxicity assessment during and after treatment completion. Data were analyzed using tools such as percentage, mean, Chi-square test and P value. Chi-square and P value was calculated by statistical online software (http://quantpsy.org). 28% of patients in study arm and 20% in control arm had complete response at 6 months after RT. Locoregional disease control was observed in 44% in study arm and 32% in control arm of patients. There was no statistical difference in grades of toxicities or overall survival (OS)/disease-free survival except persistent esophagitis Grade III seen in two patients of study arm. Study suggests that CHARTWEL in combination with NACT is an effective strategy to treat patients with locally advanced lung cancer with the advantage of a smaller dose and shorter duration. Although large multivariate studies still needed.

A prospective study of response and toxicity of induction chemotherapy followed by concurrent chemoradiation versus only concurrent chemoradiation in patients with locoregionally advanced unresectable head-and-neck cancer

Background: The first-line treatment for locally advanced squamous cell carcinoma of head-and-neck cancer is concurrent chemoradiation, which is the standard of care. Concurrent chemoradiation improved locoregional control but little impact on distance metastases. Induction chemotherapy (IC) can reduce local disease and distance metastases. Objectives: The purpose of our study is to compare the outcome of disease and toxicity between IC followed by concurrent chemo-radiation and only concurrent chemoradiation in patients of locally advanced unresectable head-and-neck cancer. Materials and Methods: A total of 37 patients were included in IC followed by concurrent chemoradiotherapy group. IC was administered with injection paclitaxel, injection carboplatin, and injection 5-fluorouracil for three cycles. Thirty-six patients were included in Arm B, concurrent chemoradiation group. The total dose of radiation was given in both the Arms 66 Gy in 33 fractions, five fractions per week for 6.3 weeks with concurrent chemotherapy injection cisplatin 40 mg/m2 weekly. Results: Grade 4 skin reaction was 2 (7%) in Arm A and 1 (3.3%) in Arm B. Grade 3 febrile neutropenia was 1 (3.4%) in Arm A and no Grade 3 febrile neutropenia was seen in Arm B. Grade 3 thrombocytopenia was 1 (3.4%) in Arm A and 2 (6.6%) in Arm B. Complete response of disease after 6 months of completion of treatment was 19 (65.5%) in Arm A and 18 (60%) in Arm B. Conclusion: Our study showed no significant difference in disease response regarding locoregional disease control between two groups but distance recurrence can be reduced with IC with manageable toxicity.

A comparison of disease recurrence between robotic versus laparotomy approach in patients with intermediate-risk endometrial cancer

ObjectiveAdvances in minimally invasive surgery, particularly with robotic surgery, have resulted in improved peri-operative outcomes in patients with endometrial cancer. In addition, randomized trials have shown that addition of adjuvant...

Intensity Modulated Radiotherapy (IMRT) With Carbon Ion Boost in the Multimodal Treatment of Salivary Duct Carcinoma.

Background: To assess outcomes and treatment related toxicity following intensity-modulated radiotherapy (IMRT) and a Carbon Ion Radiotherapy (CIRT) boost for salivary duct carcinoma (SDC).Methods: Twenty-eight consecutive patients with SDC who underwent a postoperative (82%) or definitive (18%) radiation therapy between 2010 and 2017 were assessed in this retrospective single-center analysis. CIRT boost was delivered with median 18 Gy(RBE) in 6 daily fractions, followed by an TomoTherapy®-based IMRT (median 54 Gy in 27 daily fractions). Treatment-related acute toxicity was assessed according to CTCAE Version 4.Results: Tumors were most commonly located in the major salivary glands (n = 25; 89%); 23 patients (82%) received previous surgery (R0: 30%; R1: 57%; R2: 4%; RX: 19%). Median follow-up was 30 months. Four patients (14%) experienced a local relapse and 3 (11%) developed locoregional recurrence. The two-year local control (LC) and locoregional control (LRC) was 96 and 93%, respectively. Median disease-free survival (DFS) was 27 months, metastasis-free survival (MFS) was 69 months, and overall survival (OS) was 93 months. Acute grade 3 toxicity occurred in 11 patients (mucositis, dermatitis, xerostomia; n = 2 each (7%) were the most common) and 2 osteonecroses of the mandibular (grade 3) occurred. No patients experienced grade ≥4 toxicities.Conclusions: Multimodal therapy approaches with surgery followed by IMRT and CIRT boost for SDC leads to good local and locoregional disease control. However, the frequent occurrence of distant metastases limits the prognosis and requires optimization of adjuvant systemic therapies.

The Impact of Red Blood Cell Transfusion on Mortality and Treatment Efficacy in Patients Treated with Radiation: A Systematic Review of the Literature

Introduction: Oncology patients are generally transfused to maintain a hemoglobin (Hb) above 7 g/dL (Holst et. al. BMJ 2015). Some centers use higher Hb thresholds before radiation therapy (RT) because pre-clinical data suggest that oncology patients with low hemoglobin levels may respond sub-optimally to radiation therapy due to hypoxia-induced radio-resistance (Pitson et. al. Int J Radiat Oncol Biol Phys 2001; Tatum et. al. Int J Radiat Biol 2006). It is hypothesized that higher hemoglobin levels improve tissue oxygenation, which facilitates formation of reactive oxygen species that optimize cancer cell death. No standard red blood cell transfusion thresholds have been established using interventional study data for patients with malignancies treated with radiation. This systematic review aimed to investigate the role of red blood cell (RBC) transfusion in radiation oncology patients and whether maintaining a higher Hb leads to improved overall survival, efficacy of RT on disease control and transfusion-related morbidity. Methods: We performed a literature search of PubMed, EMBASE and the Cochrane Library for randomized controlled trials, cohort studies and large case series comparing RBC transfusion thresholds in radiation oncology patients. We hand-searched references of identified articles. Eligibility criteria were studies that assessed patients receiving any RT modality for malignancy of any diagnosis and stage. Exclusion criteria were studies that did not evaluate hemoglobin or transfusion as an intervention or outcome. The primary outcome was overall survival. Secondary outcomes included locoregional tumor control, number of transfusions and adverse events associated with either radiation or transfusion. Screening and data extraction were done in duplicate. A meta-analysis was planned with outcomes presented as odds ratios with 95% confidence intervals. Results: Our search yielded 6172 titles. After exclusions, 39 articles underwent full text review (Figure 1). Only one study met the pre-specified inclusion criteria; therefore, a meta-analysis was not performed. The identified study pooled results from two Danish randomized controlled trials (DAHANCA 5 and 7) that stratified patients with head and neck squamous cell carcinoma with low pre-radiation hemoglobin levels (females <13 g/dL and males <14.5 g/dL) to RBC transfusion (235 patients) versus no transfusion (230 patients) (Hoff et. al. Acta Oncol 2011). The study found no significant differences between groups in locoregional disease control or overall survival after five years of follow up, despite increased hemoglobin levels in the transfused group. Given the search results, we expanded the review to extract data from other relevant trials not meeting inclusion criteria to conduct a narrative review of the available literature. The extracted studies involved a variety of malignancies and were primarily single-center retrospective studies assessing outcomes of local transfusion policies. Some studies featured univariate and multivariate analyses, but had conflicting results on the effects of transfusion on disease control and mortality. A major criticism of these studies was the lack of comparison between different transfusion thresholds in anemic patients. Conclusions: This systematic review illustrates the lack of data on the effect of RBC transfusion strategies in oncology patients undergoing radiation. Well-designed prospective studies are urgently needed in this area due to variability in practice. Disclosures No relevant conflicts of interest to declare.

PARP1 Inhibition Radiosensitizes Models of Inflammatory Breast Cancer to Ionizing Radiation.

Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC), with local control rates of 80% or less at 5 years. Given the unsatisfactory outcomes for these patients, there is a clear need for intensification of local therapy, including radiation. Inhibition of the DNA repair protein PARP1 has had little efficacy as a single agent in breast cancer outside of studies restricted to patients with BRCA mutations; however, PARP1 inhibition (PARPi) may lead to the radiosensitization of aggressive tumor types. Thus, this study investigates inhibition of PARP1 as a novel and promising radiosensitization strategy in IBC. In multiple existing IBC models (SUM-149, SUM-190, MDA-IBC-3), PARPi (AZD2281-olaparib and ABT-888-veliparib) had limited single-agent efficacy (IC50 > 10 μmol/L) in proliferation assays. Despite limited single-agent efficacy, submicromolar concentrations of AZD2281 in combination with RT led to significant radiosensitization (rER 1.12-1.76). This effect was partially dependent on BRCA1 mutational status. Radiosensitization was due, at least in part, to delayed resolution of double strand DNA breaks as measured by multiple assays. Using a SUM-190 xenograft model in vivo, the combination of PARPi and RT significantly delays tumor doubling and tripling times compared with PARPi or RT alone with limited toxicity. This study demonstrates that PARPi improves the effectiveness of radiotherapy in IBC models and provides the preclinical rationale for the opening phase II randomized trial of RT ± PARPi in women with IBC (SWOG 1706, NCT03598257).

Comparison of Radiation Therapy and Radical Prostatectomy in the Treatment of High-Risk Prostate Cancer: A Retrospective Matched Pair Review

Both definitive radiation therapy (RT) ±androgen deprivation therapy (ADT) and radical prostatectomy (RP) + adjuvant RT±ADT are considered standard of care treatment regimens for patients with high risk prostate cancer. The ideal modality to treat this patient population and achieve disease control while also limiting treatment related toxicity remains debated. In this study, we utilized a retrospective matched pair analysis to compare survival and overall disease control outcomes relative to primary treatment modality. 1436 pts with National Comprehensive Cancer Network defined high risk prostate cancer diagnosed between August 1992 and October 2016 at a single institution were analyzed. All those eligible were treated with RP + adjuvant RT ±ADT (n=774) or definitive RT alone ±ADT (n=660), which consisted of either high dose rate (HDR) brachytherapy boost together with pelvic external beam RT (EBRT) or dose-escalated, adaptive radiation therapy (ART). A 1:1 matched pair analysis was completed, which paired 196 pts based on three poor prognostic characteristics: pre-treatment prostate-specific antigen (PSA) ≥ 20, Gleason score ≥ 8, and clinical T stage ≥T2c. There were 98 pts in both the RT and RP cohorts for this analysis. The average age of the RT and RP groups were 66.4 years and 66.7 years respectively. The median follow-up for those treated with RP was 13.6 years, while those treated with RT was 8.96 years. 21 (21.4%) treated with RP had ≥ T2c disease, while 37 (37.7%) treated with RT had ≥T2c disease. 40.8% in both the RP and RT cohorts had Gleason score ≥ 8. 37.8% of pts had a pre-treatment PSA ≥ 20 in both the RP and RT cohorts. 5 pts (5.1%) in both the RP and RT cohorts received ADT. 37 (37.7%) in the RT cohort were treated with HDR combined with EBRT, while 61 (62.2%) of the RT cohort were treated with ART. There was no statistical difference between pts treated with RT and those treated with RP for overall survival (p =0.21), cause specific survival (p=0.28), or distant disease control (p=0.88). RT was statistically superior compared to RP in regard to locoregional control (p=0.015). When analyzing the two modalities of RT used to treat high risk prostate cancer in this patient cohort compared to RP, both ART and HDR were statistically superior compared to RP in regard to locoregional disease control (p=0.049). Based on this retrospective matched pair analysis of 196 pts with high risk prostate cancer, the addition of radical prostatectomy to locoregional RT did not improve survival or locoregional disease control rates. Neither approach was associated with improved long-term survival, and locoregional disease control was superior in pts treated with definitive RT.

Vinorelbine as a radiosensitizer in Pakistani patients with locally advanced unresectable head & neck cancer (HNC) in tertiary care hospital of Pakistan

Background: Head and neck cancer (HNC) is one of the most common cancers in Pakistan. Disease free survival in HNC remains poor due to inefficient loco-regional disease control. The aim of the present study was to assess the response rate and toxicity of concomitant vinorelbine and External radiation therapy (ERT) in advanced Head and Neck cancer in local Pakistani population. The study as per Good Clinical Practice (GCP) guidelines was conducted at the oncology department of Nishat hospital Multan from 2015 to 2017. 
 Methodology: An observational, prospective study with enrollment of 50 patients of advanced head and neck cancer was followed to analyze the outcome for radiosensitization. Primary tumor sites were tongue in 15 (30%) patients; lower lip in 6 (12%); buccal cavity in 5 (10%); cheek in 5 (10%); tonsil in 4 (8%); larynx in 6 (12%); hypopharynx in 5 (10%); and parotid in 4 (8%) patients. Initial clinical stage was: IV in 23 (46%) patients and III in 27 (54%) patients. Vinorelbine (VNB) was given at dose of 10 mg i.v. infusion weekly with ERT (3D conformal radiation plan). Response rate was evaluated after at least 8 doses. Response evaluation criteria in Solid Tumors (RECIST) was used to assess complete response (CR) and partial response (PR); progressive disease (PD) and stable disease (SD). Toxicity was assessed using common toxicity criteria version 3.0 (CTCV3.0).
 Results: 44 out of 50 patients were evaluable for response rate and toxicity. Immediate response was 90% CR. After 24 months of followup CR, PR, SD, and PD were seen in 26 (59%), 6 (13%), 7 (15%) and 6 (13%) patients respectively. Grade III mucositis and dysphagia were observed in 19 (43%) and 8 (18%) patients respectively, grade III skin rash in 14 (30%) patients, grade-II peripheral neuropathy was seen in 3 (6%) patients.
 Conclusion: The study showed that vinorelbine as a radiosensitizer in advanced HNC is a feasible option with acceptable toxicities. A large study is required to define its definite role.

Abstract 3924: PARP inhibition as a radiosensitizing strategy to improve locoregional control in inflammatory breast cancer

Abstract Purpose: Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC) with local control rates <70% at 5 years in these patients. Given the unsatisfactory outcomes, there is a clear need for intensification of local therapy, including radiation, for these patients. Inhibition of poly(adenosine diphosphate-ribose) polymerase 1 (PARP1), a DNA repair protein, represents a novel and promising strategy for radiosensitizing aggressive tumors. The purpose of this study was to investigate radiosensitization by PARP1 inhibition in IBC and to determine the mechanism of radiosensitization. Methods: Pharmacologic PARP1 inhibitors, olaparib and veliparib, were used at various concentrations (10-5 to 10-12 M). Proliferation assays were used to determine the IC50s of these inhibitors in three independent IBC cell lines (SUM 149, SUM 190, MDA-IBC-3). Clonogenic survival assays were used to determine the radiosensitization in cell lines after pharmacologic PARP inhibition (PARPi). DNA damage was quantified using γH2AX staining in IBC cell lines. Transcriptomic, protein and signaling pathway changes were measured using RNA-Seq and RPPA, respectively. In vivo tumor growth was also measured in CB17-SCID mice with varying control and treatment groups (16-20 tumors/group) that included radiation (RT) alone, olaparib alone, and RT+olaparib. Results: PARPi via olaparib and veliparib had limited single agent efficacy in all three independent IBC models with IC50 values >10 µM. Despite limited single agent efficacy, sub micromolar concentrations of PARPi with RT led to significant radiosensitization with radiation enhancement ratios of 1.20-1.35 in the same three models (500 nM in SUM 190, 500 nM in MDA-IBC-3, 2 nM in SUM 149). This effect was partially dependent on BRCA 1/2 mutational status. Radiosensitization was due, at least in part, to delayed resolution of double strand DNA (dsDNA) breaks at 12, 16, and 24 hours in all models. Additionally, this effect is mediated, at least in part, by a non-homologous end joining (NHEJ) mechanism and was not dependent on homologous recombination (HR). RNA-Seq and RPPA protein pathway data identify key pathways that regulate the radiosensitization in these IBC models. Additionally, xenograft studies show significant differences in tumor doubling and tripling times between treated and untreated tumors. Conclusion: Our study demonstrates that the PARP1 inhibition improves the therapeutic index of radiotherapy in IBC cell lines. Combined PARPi with RT leads to unresolved dsDNA breaks and decreased clonogen survival. These studies provide the rationale for a phase II randomized trial of RT +/- PARPi (olaparib) in women with IBC that has recently opened for accrual (SWOG 1706 - NCT03598257). This work was supported by a grant from Komen for the Cure and NIH T-32-GM007315. Citation Format: Anna Michmerhuizen, Andrea Pesch, Leah Moubadder, Meleah Cameron, Amanda Zhang, Nicole Hirsh, Meilan Liu, Kari Wilder-Romans, Lori J. Pierce, Reshma Jagsi, Corey Speers. PARP inhibition as a radiosensitizing strategy to improve locoregional control in inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3924.

Hypofractionated radiotherapy for early glottic cancer: a retrospective interim analysis of a single institution.

PurposeTo evaluate the results of hypofractionated radiotherapy (HFX) for early glottic cancer.Materials and MethodsEighty-five patients with cT1-2N0M0 squamous cell carcinoma of the glottis who had undergone HFX, performed using intensity-modulated radiotherapy (IMRT, n = 66) and three-dimensional conformal radiotherapy (3D CRT, n = 19) were analyzed. For all patients, radiotherapy was administered at 60.75 Gy in 27 fractions. Forty-three patients received a simultaneous integrated boost (SIB) of 2.3–2.5 Gy per tumor fraction.ResultsThe median follow-up duration was 29.9 months (range, 5.5 to 76.5 months). All patients achieved complete remission at a median of 50 days after the end of radiotherapy (range, 14 to 206 days). The 5-year rates for locoregional recurrence-free survival was 88.1%, and the 5-year overall survival rate was 86.2%. T2 stage was a prognostic factor for locoregional recurrence-free survival after radiotherapy (p = 0.002). SIB for the tumor did not affect disease control and survival (p = 0.191 and p = 0.387, respectively). No patients experienced acute or chronic toxicities of ≥grade 3. IMRT significantly decreased the dose administered to the carotid artery as opposed to 3D CRT (V35, p < 0.001; V50, p < 0.001).conclusionsPatients treated with HFX achieved acceptable locoregional disease control rates and overall survival rates compared with previous HFX studies. A fraction size of 2.25 Gy provided good disease control regardless of SIB administration.

Does systemic treatment add value to stereotactic body radiation therapy for locoregional control in head and neck squamous cell carcinoma patients?

e17505 Background: Stereotactic body radiotherapy (SBRT) has been shown to provide locoregional control in head and neck squamous cell carcinoma (HNSCC) patients (pts) who are not candidates for curative procedures due to poor performance status, comorbidities, or radiation dose limitations from prior treatment. The addition of chemotherapy (chemo) and/or cetuximab (CET) is hypothesized to improve outcomes compared to SBRT alone, but there is limited data on comparative effectiveness. We compared outcomes of pts treated with SBRT vs. SBRT + chemo and/or CET using retrospective observational data from our institution. Methods: We identified new and recurrent HNSCC pts treated with SBRT +/- systemic therapy from 2012 to 2018. Age, Charlson Comorbidity Index (CCI) and stage were recorded. Primary outcome was locoregional disease control rate based on Modified Response Evaluation Criteria in Solid Tumors on 3-month post-treatment imaging. Secondary outcome was overall survival (OS) at 1 year. Pts were divided into 4 groups: SBRT, SBRT+chemo, SBRT+CET, and SBRT+chemo+CET (cohorts A, B, C and D, respectively). Results: 90 pts with median age of 73 years and median follow-up of 11.5 months were included. 94.4% were stage III or IV, and 68.9% had recurrent disease. The most commonly utilized chemotherapy was carboplatin and paclitaxel. Cohorts A, B, C and D constituted 28.9%, 31.1%, 31.1% and 8.8% respectively. Groups were well matched except for pts in Cohort A being significantly older than those in Cohort B (74.9 vs. 68.4 years; p = 0.01). Average CCI estimated 10-year survival was 8.4%. There was a trend towards improved locoregional control at 3 months in Cohort B vs. A (57.1% vs. 34.6%, p = 0.09), and improved OS at 1 year (46.4% vs. 23.1%; p = 0.07). These trends were not observed in comparisons between other cohorts. Conclusions: Chemo + SBRT may improve disease control as well as 1 year OS in HNSCC pts who do not qualify for curative procedures. Given the younger age of pts receiving chemo, selection bias cannot be excluded. Prospective studies with larger patient cohorts are needed to further evaluate the benefits and toxicities of adding systemic treatment to SBRT in this population.

Clinical effectiveness of combined interventional therapy as a salvage modality for unresectable pancreatic carcinoma.

Although different treatment methods have been introduced to treat advanced pancreatic carcinoma, the median overall survival rate remains unsatisfactory. Theoretically, combining different treatment methods should work in synergy to enhance locoregional disease control and improve survival. Therefore, the aim of the present retrospective study was to analyze the effectiveness of combined interventional therapy compared with trans-arterial chemoembolization (TACE) or chemotherapy alone for the treatment of unresectable pancreatic carcinoma. A total of 266 patients who were undergoing treatment for unresectable pancreatic carcinoma between July 2012 and November 2015 were included in the current study. The tumor responses and 3-year overall survival rates of patients treated with combined interventional therapy (TACE combined with iodine-125 seed implantation and/or radiofrequency ablation; CIT group; n=84) were compared with those of patients treated with TACE alone (TACE group; n=59), as well as patients treated with systemic chemotherapy alone (control group; n=123). Patients in the CIT group exhibited significantly improved tumor responses compared with patients in the TACE group (51.89 vs. 30.61%; P=0.028) or control group (51.89 vs. 17.20%; P<0.001). The 3-year overall survival rate of the CIT group was also significantly higher compared with that of the TACE and control groups (P=0.0116 and P=0.0001, respectively). Furthermore, the CIT group exhibited a significantly higher overall survival rate for patients with unresectable metastatic pancreatic cancer compared with the TACE and control groups (P=0.0088 and P<0.0001, respectively), which suggests that a combination of different interventional techniques increases the survival of patients with unresectable pancreatic cancer. No life-threatening complications were observed in any treatment group. In conclusion, combined interventional therapy exhibits a good efficacy and an improved survival rate for unresectable pancreatic cancer compared with TACE alone.

Prognostic value of the non invasive procedure based on DNA methylation analysis in patients surgically treated for Oral Cancer

Prognostic value of the non invasive procedure based on DNA methylation analysis in patients surgically treated for Oral Cancer

Efficacy of external beam radiotherapy and targeted therapy with vandenanib in patients with inoperable and progressive medullary thyroid cancer

The study objectiveis to evaluate modern-era radiotherapy (external beam radiotherapy, EBRT) and target therapy (TT) outcomes for advanced medullary thyroid cancer (MTC).Materials and methods.Seventy eight consecutive patients with stage IV MTC were evaluated. All of them with relapsing locally advanced or metastatic MTC, 16 had clinically relevant mediastinal involvement, and 59 had distant metastasis; 26 patients received conformal EBRT or intensity-modulated radiotherapy in monomode, 16 patients – conformal EBRT with simultaneous TT with vandenanib, 36 patients – TT in monomode. Median EBRT dose was 60 Gy.Results.Kaplan–Meier estimates of the median overall survival rate was 14 months for radiotherapy in monomode, 48 months – for conformal EBRT + simultaneous TT with vandenanib, 50 months – for TT in monomode. EBRT and TT allows for significantly shorter periods (median 3.8 weeks), to relieve the symptoms of compression-mediated organs and structures of the neck and mediastinum than in the TT (median 10.2 weeks) (p &lt;0.001).Conclusion.EBRT and TT provided durable locoregional disease control with limited morbidity.

HIPEC with oxaliplatin for colorectal peritoneal metastasis: The end of the road?

In patients with colorectal peritoneal metastases (PM), the use of cytoreductive surgery (CRS) and HIPEC with oxaliplatin (OX) is increasingly used. The results of the recently reported randomized Prodige 7 trial failed to show a difference in overall survival between patients undergoing CRS alone versus CRS combined with HIPEC using high dose OX. The trial was not designed or powered, however, to detect a potentially clinically meaningful benefit in locoregional disease control. Here, I address some potential explanations for the lack of benefit in the Prodige 7 trial, including OX efficacy issues, adverse effects of intraperitoneal high dose glucose, and potential drawbacks of the use of hyperthermia.

Multimodality Therapy for N2 Non-Small Cell Lung Cancer: An Evolving Paradigm

Induction chemoradiation for resectable N2 non-small cell lung cancer (NSCLC) is used with the intent to optimize locoregional control, whereas induction chemotherapy given in systemic doses is meant to optimally target potential distant disease. However, the optimal preoperative treatment regimen is still unknown and practice patterns continue to vary widely. We compared multiinstitutional oncologic outcomes for N2 NSCLC from 4 experienced lung cancer treatment centers. This collaborative retrospective study unites 4 major thoracic oncology centers. Patients with N2 NSCLC undergoing surgical resection after induction chemotherapy (CxT) or concurrent chemoradiation (CxRT) were included. Primary outcomes were overall and disease-free survival (OS and DFS). 822 patients were identified (CxT= 662 and CxRT= 160). There were no differences in 5-year OS (CxT 39.9% versus CxRT 42.9%, p= 0.250) nor in DFS (CxT 28.7% versus 29.8%, p= 0.207). Recurrence rates (CxT 46.8% versus CxRT 51.6%, p= 0.282) and recurrence patterns were not significantly different (Local: CxT 9.8%versus CxRT 9.7%; and Distant: CxT 30.4% versus CxRT 33.1%, p= 0.764). There was no difference in perioperative mortality. In the analyses of patients who underwent pretreatment invasive mediastinal staging (n= 555), there were still no significant differences in OS (p= 0.341) and DFS (p= 0.455) between the 2 treatment strategies. Both treatment strategies produce equivalent and better than expected outcomes compared with historical controls for N2 NSCLC, with no differences in recurrence patterns. How these conventional therapeutic strategies will compare with those involving immunotherapy combined with surgical locoregional disease control for N2 disease remains to be determined.

Improved Overall Survival and Locoregional Disease Control With Concurrent PD-1 Pathway Inhibitors and Stereotactic Radiosurgery for Lung Cancer Patients With Brain Metastases

Despite the emerging role of programmed cell death-1 (PD-1) pathway inhibitorsfor patients with advanced lung cancer, a paucity of data are available on the activity of these agents among patients with brain metastases. We investigated the outcomes of PD-1 pathway inhibitors and stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases from lung cancer. We retrospectively reviewed the medical records of non-small-celllung cancer patients with brain metastases consecutively treated with PD-1 pathway inhibitors and SRS at our institution from 2012 to 2017. Overall survival (OS), distant brain failure (DBF), and local control (LC) were assessed using Kaplan-Meier estimates and Cox regression models. We identified 37 patients treated with SRS to 85 lesions (90.6% intact and 9.4% resected) and a median total of 7 doses of PD-1 pathway inhibitors (83.8% nivolumab, 10.8% atezolizumab, 5.4% pembrolizumab). Most lesions were treated with 18Gy in a single fraction (n=61; 71.8%). Patients treated with concurrent SRS and PD-1 pathway inhibitors had longer OS and reduced rates of DBF compared with patients treated with SRS before or after PD-1 pathway inhibitor therapy (1-year OS, 87.3% vs 70.0% vs 0%, P=.008; 1-year DBF, 38.5% vs 65.8% vs 100%, P=.042). LC was favorable among lesions treated with SRS concurrent with or after PD-1 pathway inhibitor therapy compared with before PD-1 pathway inhibitor therapy (1-year LC, 100% vs 72.3%, P=.016). Three lesions transiently enlarged after SRS and then had partially or completely resolved on follow-up imaging. Four patients required steroids for SRS-associated toxicity. No patient experienced grade ≥ 4 toxicity. Concurrent treatment with SRS and PD-1 pathway inhibitors was associated with favorable OS and locoregional disease control. This combination of therapy was well tolerated and merits further evaluation in larger cohorts in a prospective setting.