Long-term neck and shoulder function among survivors of oropharyngeal squamous cell carcinoma treated with chemoradiation as assessed with the neck dissection impairment index.

BACKGROUND: Of interest is the long-term neck and shoulder impairment of patients treated with primary chemoradiotherapy (CRT). This is important for counseling patients regarding treatment decisions when discussing primary CRT. METHODS: A cross-sectional study to identify factors that contribute to neck and shoulder dysfunction in patients treated with primary CRT. We utilized the neck dissection impairment index (NDII). Eighty-seven patients treated between 2003 and 2010, who were free of disease, responded; 24 of these 87 underwent post-CRT neck dissection. Mean interval since completion of CRT was over 5 years (62.7 months). Mean age, 63.5 years, male:female 75:12. RESULTS: Mean NDII score was 87.4 (SD 22.1, range 5-100). Multiple linear regression revealed worse NDII scores for patients with larger pre-CRT gross tumor nodal volume (GTVnodal), controlled for age, sex, body mass index (BMI), and the presence of neck dissection (p = 0.02). There were significant associations with increasing GTVnodal and "low" scores for components of the NDII that assessed neck pain (p = 0.02), neck stiffness (p = 0.01), lifting heavy objects (p = 0.02), reaching overhead (p = 0.02), and ability to do work (p = 0.02). Physical therapy (PT) was evaluated as an "anchor" but it was prescribed "as needed." Regression revealed participation in PT was associated with higher GTVnodal, lower BMI, presence of neck dissection, and female sex (p = 0.00007). CONCLUSION: GTVnodal was an independent predictor of neck and shoulder impairment. High GTVnodal was associated with increased pain and stiffness, and increased difficulty lifting heavy objects, reaching overhead, overall ability to perform work-related tasks and was associated with participation in post-treatment PT.

Neurologic late effects associated with radiologic evidence of vertebral osteoradionecrosis after salvage laryngectomy: A syndrome associated with survivors of laryngeal and hypopharyngeal cancer.

BACKGROUND: Delayed nonspecific posterior neck pain after pharyngeal instrumentation can be associated with a syndrome of rapidly progressive neurologic embarrassment. We present this cohort to help define the syndrome and aid in early detection. METHODS: We conducted a retrospective case series of 6 patients presenting from 2003 to 2012 with a history of laryngeal or hypopharyngeal squamous cell carcinoma (SCC) who underwent radiotherapy (RT) or chemoradiotherapy (CRT) followed by salvage laryngectomy. RESULTS: Posterior neck and upper back pain developed a mean of 27.5 days after instrumentation of the pharynx (reconstruction after laryngectomy or pharyngeal dilation). Myelopathy developed an average of 21.5 days after the onset of posterior neck pain. Five patients required urgent decompression. Three patients developed quadriplegia. The disease-specific mortality was 50%. CONCLUSION: There is a syndrome of late neurological effects after RT, salvage surgery, and pharyngeal instrumentation that is associated with high morbidity and mortality. © 2016 Wiley Periodicals, Inc. Head Neck 38:1187-1193, 2016.

Investigating the clinical significance of body composition changes in patients undergoing chemoradiation for oropharyngeal cancer using analytic morphomics.

BACKGROUND: The purpose is to investigate the clinical significance of body morphomics changes in stage III-IV oropharyngeal cancer patients during concurrent chemoradiotherapy (CRT). METHODS: Fifty patients who underwent CRT were selected for body composition analyses by either availability of pre/post treatment DEXA scans or a novel CT-based approach of body morphomics analysis (BMA). BMA changes (lean psoas and total psoas area) were compared to total lean body mass changes by DEXA scans using two-sample t tests. Pearson correlation was used to compare the BMA measures to head and neck specific quality of life outcomes. Cox hazards model was used to predict mortality and tumor recurrence. RESULTS: Clinically significant declines in total psoas area and lean body mass of similar magnitude were observed in both BMA and DEXA cohorts after CRT. Loss of psoas area (P < 0.05) was associated with greater frailty and mobility issues (3 out of 15 UWQOL domains). Total psoas area is more sensitive for local recurrence than weight changes and T-stage on multivariate analyses. CONCLUSIONS: BMA specifically evaluating psoas area appears to correlate with head and neck cancer quality of life physical domains. Pre- and post-treatment total psoas area at L4 appears prognostic for tumor recurrence.

Impact of xerostomia on dysphagia after chemotherapy-intensity-modulated radiotherapy for oropharyngeal cancer: Prospective longitudinal study.

BACKGROUND: The purpose of this study was to assess how xerostomia affects dysphagia. METHODS: Prospective longitudinal studies of 93 patients with oropharyngeal cancer treated with definitive chemotherapy-intensity-modulated radiotherapy (IMRT). Observer-rated dysphagia (ORD), patient-reported dysphagia (PRD), and patient-reported xerostomia (PRX) assessment of the swallowing mechanics by videofluoroscopy (videofluoroscopy score), and salivary flow rates, were prospectively assessed from pretherapy through 2 years. RESULTS: ORD grades ≥2 were rare and therefore not modeled. Of patients with no/mild videofluoroscopy abnormalities, a substantial proportion had PRD that peaked 3 months posttherapy and subsequently improved. Through 2 years, highly significant correlations were observed between PRX and PRD scores for all patients, including those with no/mild videofluoroscopy abnormalities. Both PRX and videofluoroscopy scores were highly significantly associated with PRD. On multivariate analysis, PRX score was a stronger predictor of PRD than the videofluoroscopy score. CONCLUSION: Xerostomia contributes significantly to PRD. Efforts to further decrease xerostomia, in addition to sparing parotid glands, may translate into improvements in PRD. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1605-E1612, 2016.

Limitations of the Cancer of the Prostate Risk Assessment (CAPRA) Prognostic Tool for Prediction of Metastases and Prostate Cancer-specific Mortality in Patients Treated With External Beam Radiation Therapy.

OBJECTIVES: To assess the performance of the Cancer of the Prostate Risk Assessment (CAPRA) prognostic tool for freedom-from-metastases (FFM) and cause-specific survival (CSS) in patients with localized prostate cancer treated with definitive external beam radiotherapy (EBRT), and to determine whether the performance of CAPRA is influenced by androgen deprivation therapy (ADT) use or the presence of Gleason pattern 5 (GP-5). MATERIALS AND METHODS: A total of 612 patients from a prospective database of 718 patients treated with dose-escalated EBRT from 1998 to 2008 who met CAPRA scoring criteria were included in the study. Performance of CAPRA and association of CAPRA score, GP-5 and short-term or long-term ADT use (STAD or LTAD, respectively) with FFM and CSS were evaluated using Cox models. The impact of ADT use on accuracy of the CAPRA-based CaPSURE model for CSS was assessed. The discriminatory ability of the CAPRA model and modified models incorporating GP-5 and ADT use were compared using the C-index. RESULTS: Increasing CAPRA score correlated with worse FFM and CSS, and was prognostic for FFM and CSS for the overall cohort. CAPRA showed poorer discrimination for FFM and CSS in patients treated with EBRT+LTAD than those who received EBRT alone or EBRT+STAD. The addition of GP-5 and ADT use to CAPRA score increased the predictive accuracy of the CAPRA model for both FFM (C-index 0.809 vs. 0.779, P<0.001) and CSS (C-index 0.864 vs. 0.796, P=0.003). CONCLUSIONS: The CAPRA score should be modified to incorporate GP-5 and ADT use for risk adjustment and risk prediction in prostate cancer patients who receive EBRT.

Treatment Outcomes in Very High-risk Prostate Cancer Treated by Dose-escalated and Combined-Modality Radiation Therapy.

OBJECTIVES: The aim of this study was to report treatment outcomes in patients with very high-risk prostate cancer (VHRPC) treated with dose-escalated radiotherapy. METHODS: We conducted a retrospective multi-institutional review on patients with VHRPC (those with at least 2 high-risk factors of prostate-specific antigen >20 ng/mL, Gleason score 8 to 10, or clinical T3 to T4 stage), treated with either dose-escalated external-beam radiotherapy (EBRT) or combined-modality radiotherapy (CMRT) consisting of pelvic irradiation and permanent interstitial brachytherapy. RESULTS: A total of 238 patients with VHRPC were identified. Of them, 69% of patients received EBRT and 31% received CMRT; 88% received androgen-deprivation therapy (ADT), 56% for ≥24 months (long-term ADT). The majority (69%) of patients were above 65 years old and were less likely to receive CMRT than younger patients (25% vs. 43%, P=0.006), although they did not differ from younger patients in tumor characteristics. Median follow-up was 61 months (interquartile range, 38 to 93 mo). Biochemical progression-free survival (BPFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS) for all patients at 8 years were (±SE): 50.6%±4.7%, 68.5%±4.3%, 78.7%±3.8%, respectively, and were similar for patients 65 years and below versus above 65 years old (BPFS: HR=0.88, P=0.56; DMFS: HR=0.79, P=0.40; CSS HR=0.99, P=0.99). After adjustment for patient, tumor, and treatment-related covariates on multivariate analysis, CMRT was associated with improved BPFS (HR=0.44, P=0.012) with trends for DMFS (HR=0.52, P=0.10) and CSS (HR=0.55, P=0.21), whereas long-term ADT was independently associated with improved BPFS (HR=0.40, P=0.019), CSS (HR=0.20, P=0.002), and PCSM (HR=0.25, P=0.004). CONCLUSIONS: Dose-escalated EBRT or CMRT with long-term ADT resulted in favorable clinical outcomes for patients with VHRPC.

Matted nodes: High distant-metastasis risk and a potential indication for intensification of systemic therapy in human papillomavirus-related oropharyngeal cancer.

BACKGROUND: The purpose of this study was to determine whether matted nodes uniquely identify patients with human papillomavirus (HPV)-positive oropharyngeal cancer at disproportionately high distant failure risk who may benefit from intensified systemic therapy. METHODS: One hundred seventy-eight patients with stage III/IV HPV-positive oropharyngeal cancer who completed definitive chemoradiotherapy were stratified by risk group (low-risk = T1-3/N0-2c/<10 pack-years; intermediate-risk = T1-3/N0-2c/≥10 pack-years; and high-risk = T4 or N3). Prognostic impact of matted nodes was assessed. RESULTS: At the 52-month median follow-up, event rates with and without matted nodes were: locoregional failure: 23.3% versus 12.8% (p = .16), distant failure: 50.0% versus 1.4% (p < .01), any failure: 73.3% versus 14.2% (p < .01); cause-specific mortality: 56.7% versus 5.4% (p < .01), and death: 56.7% versus 13.5% (p < .01). In multivariate analyses, including risk group and individual risk factors, matted nodes were the strongest predictor for all endpoints except locoregional failure. Among patients without matted nodes, risk-group discriminated locoregional failure (at 3 years: low-risk = 2.0%; intermediate-risk = 14.4%; and high-risk = 24.2%; p < .01), but not distant failure (low-risk = 0.0%; intermediate-risk = 2.1%; and high-risk = 3.8%; p = .53). CONCLUSION: Matted nodes portended dramatically increased distant failure and death risks in HPV-positive oropharyngeal cancer, identifying a candidate population for consideration of chemo-intensification. © 2015 Wiley Periodicals, Inc. Head Neck 38: E805-E814, 2016.

Outcomes and prognostic factors in modern era management of major salivary gland cancer.

OBJECTIVES: There is a dearth of prospective evidence regarding cancer of the major salivary glands. Outcomes and management of major salivary gland are based largely on retrospective series spanning many decades and changes in surgical, radiation, imaging and systemic therapy strategies and technique. We sought to report contemporary patterns of relapse and prognostic factors for major salivary gland cancer. MATERIALS AND METHODS: 112 patients with major salivary gland cancers underwent resection with or without adjuvant therapy between January 1997 and September 2010. Outcomes were documented with follow-up until December 2014. Survival was calculated by the Kaplan-Meier method. Log-rank test and Cox proportional hazards regression were performed with locoregional control (LRC), distant control (DC) and overall survival (OS) as the primary outcome variables. RESULTS: Median follow-up was 55.1 months. Rates of LRC for stage I/II and III/IV at five years were 95.7% and 61.9% respectively. Rates of DC at five years for stage I/II and III/IV were 93% and 56.9% respectively. Multivariate analysis identified larger tumor size, clinical nerve involvement and in parotid cancers, advanced T stage, no adjuvant radiation, and older age at diagnosis to be associated with increased risk of locoregional recurrence (all p<0.05). Distant metastasis was associated with sublingual site, degree of clinical nerve involvement, high grade, tumor size and in parotid tumors additionally deep lobe involvement on multivariate analysis (all p<0.05). CONCLUSION: Several prognostic factors were identified that may help guide decisions regarding adjuvant therapy. DM remains a significant concern in the management of this disease.

Long-term quality of life after swallowing and salivary-sparing chemo-intensity modulated radiation therapy in survivors of human papillomavirus-related oropharyngeal cancer.

PURPOSE: To evaluate long-term health-related quality of life (HRQOL) in 2 prospective studies of chemo-intensity modulated radiation therapy (chemo-IMRT) for oropharyngeal cancer (OPC). METHODS AND MATERIALS: Of 93 patients with stage III/IV OPC treated on prospective studies of swallowing and salivary organ-sparing chemo-IMRT, 69 were eligible for long-term HRQOL assessment. Three validated patient-reported instruments, the Head and Neck QOL (HNQOL) questionnaire, the University of Washington quality of life (UWQOL) questionnaire, and the Xerostomia Questionnaire (XQ), previously administered from baseline through 2 years in the parent studies, were readministered at long-term follow-up, along with the Short-Form 36. Long-term changes in HRQOL from before treatment and 2 years were evaluated. RESULTS: Forty patients (58%) with a median follow-up of 6.5 years participated, 39 of whom (97.5%) had confirmed human papillomavirus-positive OPC. Long term, no clinically significant worsening was detected in mean HRQOL scores compared with 2 years, with stable or improved HRQOL from before treatment in nearly all domains. "Moderate" or greater severity problems were uncommon, reported by 5% of patients for eating, 5% for swallowing, and 2.5% and 5% by HNQOL and UWQOL summary scores, respectively. Freedom from percutaneous endoscopic gastrostomy tube dependence and stricture dilation beyond 2 years was 97.5% and 95%, respectively. Eleven percent and 14% of patients reported "moderate" or "severe" long-term worsening in HNQOL Pain and Overall Bother domains, respectively, which were associated with mean dose to the cervical esophagus, larynx, and pharyngeal constrictors. CONCLUSIONS: At more than 6 years' median follow-up, OPC patients treated with swallowing and salivary organ-sparing chemo-IMRT reported stable or improved HRQOL in nearly all domains compared with both before treatment and 2-year follow-up. New late toxicity after 2 years was uncommon. Further emphasis on sparing the swallowing organs may yield additional HRQOL gains for long-term OPC survivors.

Bone marrow-derived stromal cell therapy in cirrhosis: clinical evidence, cellular mechanisms, and implications for the treatment of hepatocellular carcinoma.

Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local disease control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow-derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment of HCC.

Patient-reported voice and speech outcomes after whole-neck intensity modulated radiation therapy and chemotherapy for oropharyngeal cancer: prospective longitudinal study.

PURPOSE: To describe voice and speech quality changes and their predictors in patients with locally advanced oropharyngeal cancer treated on prospective clinical studies of organ-preserving chemotherapy-intensity modulated radiation therapy (chemo-IMRT). METHODS AND MATERIALS: Ninety-one patients with stage III/IV oropharyngeal cancer were treated on 2 consecutive prospective studies of definitive chemoradiation using whole-field IMRT from 2003 to 2011. Patient-reported voice and speech quality were longitudinally assessed from before treatment through 24 months using the Communication Domain of the Head and Neck Quality of Life (HNQOL-C) instrument and the Speech question of the University of Washington Quality of Life (UWQOL-S) instrument, respectively. Factors associated with patient-reported voice quality worsening from baseline and speech impairment were assessed. RESULTS: Voice quality decreased maximally at 1 month, with 68% and 41% of patients reporting worse HNQOL-C and UWQOL-S scores compared with before treatment, and improved thereafter, recovering to baseline by 12-18 months on average. In contrast, observer-rated larynx toxicity was rare (7% at 3 months; 5% at 6 months). Among patients with mean glottic larynx (GL) dose ≤20 Gy, >20-30 Gy, >30-40 Gy, >40-50 Gy, and >50 Gy, 10%, 32%, 25%, 30%, and 63%, respectively, reported worse voice quality at 12 months compared with before treatment (P=.011). Results for speech impairment were similar. Glottic larynx dose, N stage, neck dissection, oral cavity dose, and time since chemo-IMRT were univariately associated with either voice worsening or speech impairment. On multivariate analysis, mean GL dose remained independently predictive for both voice quality worsening (8.1%/Gy) and speech impairment (4.3%/Gy). CONCLUSIONS: Voice quality worsening and speech impairment after chemo-IMRT for locally advanced oropharyngeal cancer were frequently reported by patients, underrecognized by clinicians, and independently associated with GL dose. These findings support reducing mean GL dose to as low as reasonably achievable, aiming at ≤20 Gy when the larynx is not a target.

Refining risk stratification for locoregional failure after chemoradiotherapy in human papillomavirus-associated oropharyngeal cancer.

BACKGROUND: To determine whether the addition of molecular and imaging biomarkers to established clinical risk factors could help predict locoregional failure (LRF) after chemoradiation in human papillomavirus (HPV)-related (+) oropharyngeal cancer (OPC) and improve patient selection for locoregional treatment de-intensification. METHODS: HPV status was determined for 198 consecutive patients with stage III/IV OPC treated with definitive chemoradiation from 5/2003 to 10/2010. The impact of pre-therapy epidermal growth factor receptor (EGFR) overexpression; imaging biomarkers including primary tumor and nodal maximum standardized uptake values on FDG-PET, gross tumor volumes, and matted nodes; and clinical factors on LRF (including residual disease at adjuvant neck dissection) was assessed. RESULTS: Primary tumors were HPV+ in 184 patients and HPV-negative in 14. EGFR overexpression was related to HPV-negative status and was univariately associated with LRF in the overall population, but was neither retained in the multivariate model after adjustment for HPV status, nor associated with LRF in HPV+ patients. Similarly, imaging biomarkers were univariately associated with LRF, but correlated with T-stage and/or N-stage and did not remain predictive in HPV+ patients after adjustment for T4- and N3-stages, which were the only significant predictors of LRF on multivariate analysis. Among HPV+ patients with non-T4- or N3-stages, only minimal smoking was associated with decreased LRF. CONCLUSIONS: The prognostic impact of EGFR overexpression and imaging biomarkers on LRF was predominantly related to their association with HPV-negative status and T- or N-stage, respectively. Among HPV+ OPC patients treated with uniform chemoradiation, only T4-stage, N3-stage, and smoking contributed to risk-stratification for LRF.

Reliability of post-chemoradiotherapy F-18-FDG PET/CT for prediction of locoregional failure in human papillomavirus-associated oropharyngeal cancer.

OBJECTIVES: Although widely adopted, the accuracy of post-chemoradiotherapy (CRT) 18F-fluorodeoxygluocose positron emission tomography/computed tomography (PET/CT) for predicting locoregional failure (LRF) in human papillomavirus-related (HPV+) oropharyngeal cancer (OPC) remains poorly characterized. We assessed the predictive value of 3-month PET/CT response for LRF in this population. MATERIALS AND METHODS: 101 consecutive patients with stage III-IV HPV+ OPC who underwent definitive CRT with pre-treatment and 3-month post-CRT PET/CT at our institution from 3/2005-3/2011 were included. 3-month PET/CT response was re-classified as complete-response (CR), near-CR, or incomplete-response (

Head and neck squamous cell carcinoma of unknown primary: neck dissection and radiotherapy or definitive radiotherapy.

BACKGROUND: Management of head and neck carcinoma from unknown primary (HNCUP) remains controversial, with neck dissection and radiotherapy (RT) or definitive RT both commonly used. The purpose of this study was to characterize HNCUP and retrospectively compare outcomes for patients treated with neck dissection + RT versus definitive RT. METHODS: From 1994 to 2009, 41 patients with HNCUP underwent either neck dissection + RT (n = 22) or definitive RT ± concurrent chemotherapy (n = 19) at our institution. Treatment outcomes were compared using Kaplan-Meier methods and log-rank test. RESULTS: There were no differences between patients treated with neck dissection + RT and definitive RT in overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), freedom from locoregional failure (FFLRG), or freedom from distant failure (FFDF). Among 17 patients who underwent neck dissection + RT for whom human papillomavirus (HPV) status could be determined, HPV(+) patients trended toward improved OS (p = .06) and PFS (p = .15). CONCLUSION: Neck dissection and postoperative RT resulted in similar outcomes as definitive RT. The prognostic implications of HPV(+) nodes in HNCUP are similar to those in oropharyngeal primary cancers.

Chemoselection: a paradigm for optimization of organ preservation in locally advanced larynx cancer.

Definitive chemoradiation (CRT) and laryngectomy followed by postoperative radiotherapy (RT) are both considered standard-of-care options for the management of advanced laryngeal cancer. While organ preservation with chemoradiotherapy is often the preferred up-front approach for appropriately selected candidates, the functional benefits of organ preservation must be carefully balanced against the considerable morbidity of salvage laryngectomy in patients who fail primary chemoradiation. Up-front identification of patients who are likely to require surgical salvage, therefore, is an important aim of any organ preserving approach in order to minimize morbidity while maximizing organ preservation. To this end, a strategy of 'chemoselection', using the primary tumor's response after 1 cycle of induction chemotherapy as an in vivo method of selecting responders for definitive chemoradiation while reserving primary surgical management for non-responders, has been employed extensively at our institution. The rationale, treatment results and future directions of this approach are discussed.

Interval to biochemical failure predicts clinical outcomes in patients with high-risk prostate cancer treated by combined-modality radiation therapy.

PURPOSE: To validate the prognostic value of interval to biochemical failure (IBF) in patients with high-risk prostate cancer (HiRPCa) treated with combined-modality radiation therapy (CMRT) with or without androgen deprivation therapy (ADT). METHODS AND MATERIALS: We conducted a retrospective review of HiRPCa (prostate-specific antigen >20 ng/mL, Gleason score [GS] 8-10, or clinical T stage T3-T4) treated with either dose-escalated external beam radiation therapy (EBRT) or CMRT. Interval to biochemical failure was classified as ≤18 or >18 months from the end of all therapy to the date of biochemical failure (BF). Kaplan-Meier methods and Cox proportional hazards regression were used to evaluate the prognostic value of IBF ≤18 months for distant metastasis (DM) and prostate cancer-specific mortality (PCSM). RESULTS: Of 958 patients with a median follow-up of 63.2 months, 175 patients experienced BF. In those with BF, there were no differences in pretreatment clinical characteristics between the EBRT and CMRT groups, except for a higher proportion of patients with GS 8-10 in the CMRT group (70% vs 52%, P=.02). Median IBF after all therapy was 24.0 months (interquartile range 9.6-46.0) in the EBRT group and 18.9 months (interquartile range 9.2-34.5) in the CMRT group (P=.055). On univariate analysis, IBF ≤18 months was associated with increased risk of DM and PCSM in the entire cohort and the individual EBRT and CMRT groups. On multivariate analysis, only GS 9-10 and IBF ≤18 months, but not the radiation therapy regimen or ADT use, predicted DM (hazard ratio [HR] 3.7, P<.01, 95% confidence interval [CI] 1.4-10.3 for GS 9-10; HR 3.9, P<.0001, 95% CI 2.4-6.5 for IBF ≤18 months) and PCSM (HR 14.8, P<.009, 95% CI 2.0-110 for GS 9-10; HR 4.4, P<.0001, 95% CI 2.4-8.1 for IBF ≤18 months). CONCLUSIONS: Short IBF was highly prognostic for higher DM and PCSM in patients with HiRPCa. The prognostic value of IBF for DM and PCSM was not affected by the radiation therapy regimen or ADT use.

Prognostic significance of carbohydrate antigen 19-9 in unresectable locally advanced pancreatic cancer treated with dose-escalated intensity modulated radiation therapy and concurrent full-dose gemcitabine: analysis of a prospective phase 1/2 dose escalation study.

PURPOSE: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. METHODS AND MATERIALS: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. RESULTS: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤ 90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). CONCLUSIONS: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.