Analysis of Relapse Events After Definitive Chemoradiotherapy in Locally Advanced Non-Small-Cell Lung Cancer Patients.

BACKGROUND: The appropriate follow-up frequency after definitive chemoradiotherapy (CRT) for locally advanced non-small-cell lung cancer patients is unknown. Although surveillance guidelines have been proposed, very few data support current recommendations. Here we analyze relapse events after CRT and investigate whether symptomatic relapses versus those detected by surveillance imaging influences outcomes. PATIENTS AND METHODS: Stage III non-small-cell lung cancer patients treated with CRT at our institution between 2005 and 2014 were retrospectively analyzed. Relapse events were grouped into posttreatment intervals and analyzed with cumulative tables. Time to relapse and overall survival (OS) were compared between patients with relapse detection via symptomatic presentation versus surveillance imaging. RESULTS: A total of 211 patients were identified for analysis. The median follow-up was 43 months for patients alive at the time of analysis. The median age was 63 years, and equal proportions had IIIA or IIIB disease. A total of 135 patients (64%) experienced disease relapse, and of these, 74% did so within 12 months. In those who did not experience relapse at ≤ 12 months, 16%, 6%, and < 5% experienced relapse during 12 to 24, 24 to 36, and > 36 months of follow-up, respectively. In patients with relapse, 56% presented symptomatically, which led to inferior median OS compared to those identified by surveillance imaging (23 vs. 36 months; P = .013). CONCLUSION: This study identified that most relapses occur within 1 year of completing CRT, and approximately half of these occur within 6 months. A symptomatic relapse led to inferior OS. More aggressive surveillance imaging may therefore identify asymptomatic relapses that are amenable to earlier salvage therapy.

Patient choice for high-volume center radiation impacts head and neck cancer outcome.

BACKGROUND: Studies suggest treatment outcomes may vary between high (HVC)- and low-volume centers (LVC). Radiation therapy (RT) for head and neck cancer (HNC) requires weeks of treatment, the inconvenience of which may influence a patient's choice for treatment location. We hypothesized that receipt of RT for HNC at a HVC would influence outcomes compared to patients evaluated at a HVC, but who chose to receive RT at a LVC. METHODS: From 1998 to 2011, 1930 HNC patients were evaluated at a HVC and then treated with RT at either a HVC or LVC. Time-to-event outcomes and treatment factors were compared. RESULTS: Median follow-up was 34 months. RT was delivered at a HVC for 1368 (71%) patients and at a LVC in 562 (29%). Patients were more likely to choose HVC-RT if they resided in the HVC's county or required definitive RT (all P < 0.001). HVC-RT was associated with a significant improvement in 3-year LRC (84% vs 68%), DFS (68% vs 48%), and OS (72% vs 57%) (all P < 0.001). On multivariate analysis (MVA), HVC-RT independently predicted for improved LRC, DFS, and OS (all P < 0.05). CONCLUSIONS: In patients evaluated at a HVC, the choice of RT location was primarily influenced by their residing distance from the HVC. HVC-RT was associated with improvements in LRC, DFS, and OS in HNC. As treatment planning and delivery are technically demanding in HNC, the choice to undergo treatment at a HVC may result in more optimal delivered dose, RT duration, and outcome.

Viral hepatitis associated hepatocellular carcinoma outcomes with yttrium-90 radioembolization.

BACKGROUND: Viral associated (VA) malignancies have recently been correlated with improved outcomes. We sought to evaluate outcomes of patients with hepatocellular carcinoma (HCC) with and without viral hepatitis (hepatitis B and C) treated with lobar yttrium-90 radioembolization (Y-90 RE). METHODS: After IRB approval, an institutional database of patients with HCC who received RE between 2009-2014 was queried and 99 patients were identified that received a total of 122 lobar RE. Charts were reviewed to capture previous treatments, viral hepatitis status, α-fetoprotein values (AFP), Child-Pugh class (CP), albumin-bilirubin score (ALBI), portal vein thrombosis (PVT), volumes treated and doses delivered. Comparison was made with Chi-square and Mann-Whitney U test. Intrahepatic control (IHC), extrahepatic control (EHC), progression free survival (PFS), and overall survival (OS) were calculated according to the Kaplan-Meier method stratified by cause of underlying liver disease (viral vs. non-viral) and survival differences were assessed via the log-rank test. Hazard ratios were calculated using Cox regression. RESULTS: Median follow up for VA HCC and non-VA (NVA) HCC patients was 10.9 months (range, 0.8-46.7 months) and 11.8 months (range, 1.1-62.8 months), respectively. Patients with VA HCC (n=44) were younger (P<0.001) and had smaller pretreatment liver volumes (P<0.001); however, there was no difference with respect to gender, pre-treatment AFP, CP, ALBI, PVT, extrahepatic disease, previous treatment, or dose delivered. Median doses for VA and NVA HCC patients were 129.5 Gy (range, 90-215.8 Gy) and 131 Gy (range, 100.9-265 Gy), respectively (P=0.75). One year IHC showed a strong trend to better control for VA HCC at 67% versus 34% for NVA HCC (P=0.067) but 1 year EHC was significantly worse at 63% for VA HCC versus 86% for NVA HCC (P=0.027). There were no significant differences in survival, with a 1-year PFS of 45% for VA HCC versus 31% for NVA HCC (P=0.56) and 1 year OS of 46% versus 55% (P=0.55). Patients that received salvage treatments, CP A, no PVT, and those without extrahepatic disease had improved OS. CONCLUSIONS: Patients with VA HCC had a trend to improved IHC and significantly worse EHC. Prospective investigation of novel systemic therapies following Y-90 RE in patients with VA HCC is warranted to potentially further extend survival in VA HCC patients by addressing extra-hepatic disease.

Low-dose-rate Brachytherapy for Prostate Cancer in Low-resource Settings.

PURPOSE: In areas with limited health care, it is important to identify and implement effective treatment methods and to optimize available resources. We investigated the implementation of a low-dose-rate (LDR) brachytherapy program for the treatment of prostate cancer (PCa) in a low-resource setting such as Puerto Rico (PR), where PCa is the main cause of cancer-associated death. METHODS AND MATERIALS: After institutional approval, the medical records of patients with nonmetastatic PCa undergoing LDR brachytherapy from 2008 to 2013 were reviewed from PR. The factors analyzed included adequate D90 (radiation dose delivered to 90% of the target volume) coverage (≥140 Gy), early and late toxicity (Common Terminology Criteria for Adverse Events grade >2), and prostate-specific antigen failure. Freedom from biochemical failure was evaluated using Kaplan-Meier analysis. RESULTS: The barriers to implementation of LDR brachytherapy in a country with limited resources were identified. These included lack of access to funding for startup costs, specific referral patterns, lack of trained support staff, such as dosimetrists and physicists, and initial opposition from insurance companies for reimbursement. The initial results from 191 patients were included in the present study with a median follow-up period of 26 months. Prostate-specific antigen failure occurred in 6 patients (3%). No early or late gastrointestinal toxicity (grade >2) developed. Only 3 (2%) and 2 (1%) patients experienced early and late genitourinary toxicity (grade >2), respectively. The 2- and 3-year freedom from biochemical failure in this population was 97% and 95.9%, respectively. CONCLUSIONS: At present, limited data are available delineating the barriers faced by low-resource settings in the implementation of LDR brachytherapy. Our data highlight the issues unique to this environment and support the use of LDR brachytherapy as a reliable and effective treatment modality for patients with PCa in low-resource settings.

Quality of Life after post-prostatectomy intensity modulated radiation therapy to the prostate bed with or without the use of gold fiducial markers for image guidance or higher total radiotherapy doses

ABSTRACT Purpose To evaluate quality of life (QoL) after post-prostatectomy intensity modulated radiation therapy (IMRT) in the "adjuvant" setting starting within 4 months of radical prostatectomy for adverse features; and "salvage" setting for a PSA≥0.2ng/mL. Materials and Methods Retrospective review of 130 patients who underwent IMRT to the prostate bed±gold fiducial marker placement for image guidance to 64.8-72.0Gy (median, 70.2Gy) between 2004 and 2013. Higher doses were defined as 70.2-72.0Gy and lower doses were defined as 64.8-68.4Gy. Androgen deprivation therapy (ADT) was given to 4/48 (8%) adjuvant patients and 9/82 (11%) salvage patients. International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM), and Expanded Prostate Cancer Index Composite-26-bowel (EPIC-26-bowel) questionnaires were used to assess urinary, sexual, and bowel QoL, respectively. Results Median follow-up was 46 months. There were better urinary (p=0.03) and sexual (p=0.002) QoL scores with adjuvant IMRT relative to salvage IMRT. The use of prostate bed fiducial markers did not significantly affect urinary, sexual, or bowel QoL (p=0.39, p=0.49, and p=0.40, respectively). Higher total radiotherapy doses did not significantly affect urinary, sexual, or bowel QoL (p=0.21, p=0.61, and p=0.36, respectively). Conclusions There was no significant change in urinary, sexual, and bowel sexual QoL with post-prostatectomy IMRT regardless of whether prostate bed fiducial markers or higher total radiotherapy doses were used. QoL with IMRT in the present study compares favorably with prior reports for three-dimensional conformal radiation therapy.

Quality of Life after post-prostatectomy intensity modulated radiation therapy to the prostate bed with or without the use of gold fiducial markers for image guidance or higher total radiotherapy doses.

PURPOSE: To evaluate quality of life (QoL) after post-prostatectomy intensity modulated radiation therapy (IMRT) in the "adjuvant" setting starting within 4 months of radical prostatectomy for adverse features; and "salvage" setting for a PSA≥0.2ng/mL. MATERIALS AND METHODS: Retrospective review of 130 patients who underwent IMRT to the prostate bed±gold fiducial marker placement for image guidance to 64.8-72.0Gy (median, 70.2Gy) between 2004 and 2013. Higher doses were defined as 70.2-72.0Gy and lower doses were defined as 64.8-68.4Gy. Androgen deprivation therapy (ADT) was given to 4/48 (8%) adjuvant patients and 9/82 (11%) salvage patients. International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM), and Expanded Prostate Cancer Index Composite-26-bowel (EPIC-26-bowel) questionnaires were used to assess urinary, sexual, and bowel QoL, respectively. RESULTS: Median follow-up was 46 months. There were better urinary (p=0.03) and sexual (p=0.002) QoL scores with adjuvant IMRT relative to salvage IMRT. The use of prostate bed fiducial markers did not significantly affect urinary, sexual, or bowel QoL (p=0.39, p=0.49, and p=0.40, respectively). Higher total radiotherapy doses did not significantly affect urinary, sexual, or bowel QoL (p=0.21, p=0.61, and p=0.36, respectively). CONCLUSIONS: There was no significant change in urinary, sexual, and bowel sexual QoL with post-prostatectomy IMRT regardless of whether prostate bed fiducial markers or higher total radiotherapy doses were used. QoL with IMRT in the present study compares favorably with prior reports for three-dimensional conformal radiation therapy.

Staged reconstruction brachytherapy has lower overall cost in recurrent soft-tissue sarcoma.

PURPOSE: Adjuvant brachytherapy (AB) with immediate (IR) and staged reconstruction (SR) are distinct treatment modalities available for patients with recurrent soft tissue sarcoma (STS). Although SR may offer local control and toxicity benefit, it requires additional upfront procedures, and there is no evidence that it improves overall survival. With the importance of value-based care, our goal is to identify which technique is more cost effective. MATERIAL AND METHODS: A retrospective review of 22 patients with recurrent extremity STS treated with resection followed by AB alone. Hospital charges were used to compare the cost between SR and IR at the time of initial treatment, at 6-month intervals following surgery, and cumulative cost comparisons at 18 months. RESULTS: Median follow-up was 31 months. Staged reconstruction (n = 12) was associated with an 18-month local control benefit (85% vs. 42%, p = 0.034), compared to IR (n = 10). Staged reconstruction had a longer hospital stay during initial treatment (10 vs. 3 days, p = 0.002), but at 18 months, the total hospital stay was no longer different (11 vs. 11 days). Initially, there was no difference in the cost of SR and IR. With longer follow-up, cost eventually favored SR, which was attributed primarily to the costs associated with local failure (LF). On multivariate analysis, cost of initial treatment was associated with length of hospital stay (~$4.5K per hospital day, p < 0.001), and at 18 months, the cumulative cost was ~175K lower with SR (p = 0.005) and $58K higher with LF (p = 0.02). CONCLUSIONS: In recurrent STS, SR has a longer initial hospital stay when compared to IR. At 18 months, SR had lower rates of LF, translating to lower total costs for the patient. SR is the more cost-effective brachytherapy approach in the treatment of STS, and should be considered as healthcare transitions into value-based medicine.

The impact of body mass index on dosimetric quality in low-dose-rate prostate brachytherapy.

PURPOSE: Low-dose-rate (LDR) brachytherapy has been established as an effective and safe treatment option for men with low and intermediate risk prostate cancer. In this retrospective analysis, we sought to study the effect of body mass index (BMI) on post-implant dosimetric quality. MATERIAL AND METHODS: After institutional approval, records of patients with non-metastatic prostate cancer treated in Puerto Rico with LDR brachytherapy during 2008-2013 were reviewed. All patients were implanted with 125I seeds to a prescription dose of 145 Gy. Computed tomography (CT) based dosimetry was performed 1 month after implant. Patients with at least 1 year of prostate-specific antigen (PSA) follow-up were included. Factors predictive of adequate D90 coverage (≥ 140 Gy) were compared via the Pearson χ2 or Wilcoxon rank-sum test as appropriate. RESULTS: One-hundred and four patients were included in this study, with 53 (51%) patients having a D90 ≥ 140 Gy. The only factor associated with a dosimetric coverage detriment (D90 < 140 Gy) was BMI ≥ 25 kg/m2 (p = 0.03). Prostate volume (p = 0.26), initial PSA (p = 0.236), age (p = 0.49), hormone use (p = 0.93), percent of cores positive (p = 0.95), risk group (p = 0.24), tumor stage (p = 0.66), and Gleason score (p = 0.61) did not predict D90. CONCLUSIONS: In this study we show that BMI is a significant pre-implant predictor of D90 (< 140 Gy vs. ≥ 140 Gy). Although other studies have reported that prostate volume also affects D90, our study did not find this correlation to be statistically significant, likely because all of our patients had a prostate volume < 50 cc. Our study suggests that in patients with higher BMI values, more rigorous peri-implant dosimetric parameters may need to be applied in order to achieve a target D90 > 140 Gy.

Treatment delays, race, and outcomes in head and neck cancer.

PURPOSE: Patient race has been shown to predict for differences in outcomes and has been attributed to socioeconomic factors such as social support and access to healthcare. In head and neck cancer (HNC), a disease without recommended screening, we sought to investigate the association between race, treatment delays and outcome. METHODS: Records of 1802 patients with non-metastatic squamous cell HNC treated between 1998 and 2013 were retrospectively assessed from an institutional database. Patient demographics, tumor and treatment characteristics, and patient outcomes were abstracted from the chart. Differences between groups were assessed via logistic regression multivariate analysis (MVA). Outcomes including locoregional control (LRC) and overall survival (OS) were then estimated via Kaplan-Meier and Cox-regression MVA. RESULTS: Median follow up was 34 months. Patient races included white (n=1671, 93%), black (n=80, 4%), Asian (n=18, 1%), and other (n=33, 2%). On logistic regression MVA, Black patients were less likely to be married (39% vs. 63%; OR 0.5 95%CI 0.30-0.83, p=0.007) or be currently employed (43% vs. 61%; OR 0.44 95%CI 0.26-0.74, p=0.002) when compared to non-blacks. Black patients were also younger (54 vs. 59 years, p=0.001), more likely to present with advanced tumor stage (T4: 48% vs. 25%), and more often had >45days elapsed from diagnosis to treatment initiation (DTI) (61% vs. 49%, p=0.028). Delays in treatment, such as delayed diagnosis (advanced disease presentation) and delays in DTI>45days were also associated with marital and employment status. Black patients were associated with a lower 3-year LRC rate (65% vs. 81%, p<0.001) and OS rate (43% vs. 69%, p<0.001), compared to non-black patients. Patients with >45days DTI had a detriment in 3-year LRC (77% vs. 83%, p=0.002) and OS (66% vs. 69%, p=0.009). On Cox MVA, black race was independently prognostic for worse LRC (HR 1.62 95%CI 1.04-2.51, p=0.033) and OS (HR 1.55 95%CI 1.15-2.08, p=0.004) vs. non-blacks. CONCLUSION: Black race is independently prognostic for LRC and OS. Delays in HNC treatment, such as more advanced tumor stage presentation and delays in treatment initiation, may be attributed to socioeconomic factors such as employment status and social support. Efforts to accommodate these factors may expedite treatment, in hopes of improving the race related outcome disparity in HNC.

Having Medicaid insurance negatively impacts outcomes in patients with head and neck malignancies.

BACKGROUND: Patients covered by Medicaid insurance appear to have poorer cancer outcomes. Herein, the authors sought to test whether Medicaid was associated with worse outcomes among patients with head and neck cancer (HNC). METHODS: The records of 1698 patients with squamous cell HNC without distant metastatic disease were retrospectively reviewed from an institutional database between 1998 and 2011. At the time of diagnosis, insurance status was categorized as Medicaid, Medicare/other government insurance, or private insurance. Outcomes including locoregional control (LRC) and overall survival (OS) were estimated using the Kaplan-Meier method and Cox regression multivariate analysis (MVA). RESULTS: The median follow-up for all patients was 35 months. Medicaid patients comprised 11% of the population; the remaining patients were privately insured (56%) or had Medicare/government insurance (34%). On MVA, Medicaid patients were younger, were current smokers, had higher tumor T and N classifications, and experienced a longer time from diagnosis to treatment initiation (all P<.005). Medicaid insurance status was associated with a deficit of 13% in LRC (69% vs 82%) and 26% in OS (46% vs 72%) at 3 years (all with P<.001). A time from diagnosis to treatment initiation of >45 days was found to be associated with worse 3-year LRC (77% vs 83%; P = .009) and OS (68% vs 71%; P = .008). On MVA, Medicaid remained associated with a deficit in LRC (P = .002) and OS (P<.001). CONCLUSIONS: Patients with Medicaid insurance more often present with locally advanced HNC and experience a higher rate of treatment delays compared with non-Medicaid patients. Medicaid insurance status appears to be independently associated with deficits in LRC and OS. Improvements in the health care system, such as expediting treatment initiation, may improve the outcomes of patients with HNC. Cancer 2016;122:3529-3537. © 2016 American Cancer Society.

Management of Oropharyngeal Cancer in the HPV Era.

BACKGROUND: Historically, oropharyngeal cancer (OPC) has been attributed to risk factors such as smoking and alcohol use. The increased incidence of OPC has been driven by human papillomavirus (HPV) infection. METHODS: A search of the literature involving HPV infection and OPC was performed, along with a search of ongoing clinical trials regarding HPV-positive OPC. RESULTS: This review summarizes the differences in epidemiology and prognosis of HPV-positive OPC compared with non-HPV-related OPC. It will also discuss use of de-escalating treatment to minimize toxicity while maintaining excellent outcomes. Disease management is also addressed, including prevention and follow-up recommendations for this cohort of patients. CONCLUSIONS: HPV-positive OPC is a distinct disease, and efforts should be made to personalize its management. Preventive measures and vaccinations, along with de-escalation of treatment, may help optimize outcomes in this population.

Radiosensitivity Differences Between Liver Metastases Based on Primary Histology Suggest Implications for Clinical Outcomes After Stereotactic Body Radiation Therapy.

PURPOSE/OBJECTIVES: Evidence from the management of oligometastases with stereotactic body radiation therapy (SBRT) reveals differences in outcomes based on primary histology. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and assessed our clinical outcomes after SBRT based on primary histology. METHODS AND MATERIALS: Patients were identified from our prospective, observational protocol. The previously tested RSI 10 gene assay was run on samples and calculated using the published algorithm. An independent cohort of 33 patients with 38 liver metastases treated with SBRT was used for clinical correlation. RESULTS: A total of 372 unique metastatic liver lesions were identified for inclusion from our prospective, institutional metadata pool. The most common primary histologies for liver metastases were colorectal adenocarcinoma (n=314, 84.4%), breast adenocarcinoma (n=12, 3.2%), and pancreas neuroendocrine (n=11, 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were gastrointestinal stromal tumor (0.57), melanoma (0.53), colorectal neuroendocrine (0.46), pancreas neuroendocrine (0.44), colorectal adenocarcinoma (0.43), breast adenocarcinoma (0.35), lung adenocarcinoma (0.31), pancreas adenocarcinoma (0.27), anal squamous cell cancer (0.22), and small intestine neuroendocrine (0.21) (P<.0001). The 12-month and 24-month Kaplan-Meier rates of local control (LC) for colorectal lesions from the independent clinical cohort were 79% and 59%, compared with 100% for noncolorectal lesions (P=.019), respectively. CONCLUSIONS: In this analysis, we found significant differences based on primary histology. This study suggests that primary histology may be an important factor to consider in SBRT radiation dose selection.

Implications of staged reconstruction and adjuvant brachytherapy in the treatment of recurrent soft tissue sarcoma.

PURPOSE: Prior studies illustrated a reduction in wound complications with the use of staged reconstruction (SR) and negative pressure wound therapy when treating soft tissue sarcoma (STS) with surgical resection followed by high-dose-rate adjuvant brachytherapy. The purpose of this study is to compare the outcomes of SR and immediate reconstruction (IR) brachytherapy in recurrent STS. METHODS AND MATERIALS: A retrospective review of 40 patients with recurrent STS of the local extremity and trunk treated with resection followed by adjuvant brachytherapy alone. Margin status was defined as positive (SM(+)) if there was microscopic involvement (R1) or ≤1 mm margin and negative (SM(-)) if >1 mm margin was obtained. SR and IR were compared regarding toxicity, local control, and limb preservation. RESULTS: Median followup was 27 months. When comparing the SR (n = 22) and IR (n = 18) cohorts, there was a significantly lower final SM(+) rate in SR (32% vs. 83%, p < 0.01). A 2-year local control benefit seen with SR (80% vs. 34%; p = 0.012) and a final SM(-) (81% vs. 39%; p = 0.023). SR was associated with less toxicity on multivariate analysis, including a 90% decrease in persistent edema, an 80% decrease in wound dehiscence, and a 94% decrease in nonhealing wounds, when compared to IR. Ten of 31 (32%) extremity cases required eventual amputation from either chronic wound complications (n = 4) or local recurrence (n = 6). SR predicted for a benefit in 2-year limb preservation (88% vs. 50%; p = 0.008). CONCLUSION: In our series, the treatment with SR brachytherapy resulted in less morbidity and an improved final SM(-) rate. This technique translated to an improvement in both local control and limb preservation of recurrent STS.