Pretreatment metabolic tumor volume as a prognostic factor in HPV-associated oropharyngeal cancer in the context of AJCC 8th edition staging.

BACKGROUND: This study evaluates the prognostic significance of 18 F-fluorodeoxyglucose-positron emission tomography ([F-18]FDG-PET)-derived metabolic tumor volume (MTV) in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) in the context of AJCC 8th edition staging. METHODS: We performed a retrospective study of HPV-associated OPSCCs treated with postoperative or definitive radiation. The prognostic significance of pretreatment MTV for freedom from recurrence (FFR), freedom from distant metastasis (FFDM), and overall survival (OS) was determined using Kaplan-Meier analysis. Multivariate analysis (MVA) was performed using Cox regression. RESULTS: In this 153-patient cohort, stratifying by the optimum MTV (24 cm3 ) was prognostic for FFR (P = .0002), FFDM (P = .001), and OS (P < .0001). Metabolic tumor volume (MTV) was prognostic of FFR in AJCC 8th edition stage I/II (P = .03), and stage III patients (P = .04). On multivariate analysis only MTV was a significant factor for OS. CONCLUSION: Metabolic tumor volume (MTV) is a significant prognostic factor in HPV-associated OPSCCs, independent of AJCC 8th edition stage.

Influence of respiratory motion management technique on radiation pneumonitis risk with robotic stereotactic body radiation therapy.

PURPOSE/OBJECTIVES: For lung stereotactic body radiation therapy (SBRT), real-time tumor tracking (RTT) allows for less radiation to normal lung compared to the internal target volume (ITV) method of respiratory motion management. To quantify the advantage of RTT, we examined the difference in radiation pneumonitis risk between these two techniques using a normal tissue complication probability (NTCP) model. MATERIALS/METHOD: 20 lung SBRT treatment plans using RTT were replanned with the ITV method using respiratory motion information from a 4D-CT image acquired at the original simulation. Risk of symptomatic radiation pneumonitis was calculated for both plans using a previously derived NTCP model. Features available before treatment planning that identified significant increase in NTCP with ITV versus RTT plans were identified. RESULTS: Prescription dose to the planning target volume (PTV) ranged from 22 to 60 Gy in 1-5 fractions. The median tumor diameter was 3.5 cm (range 2.1-5.5 cm) with a median volume of 14.5 mL (range 3.6-59.9 mL). The median increase in PTV volume from RTT to ITV plans was 17.1 mL (range 3.5-72.4 mL), and the median increase in PTV/lung volume ratio was 0.46% (range 0.13-1.98%). Mean lung dose and percentage dose-volumes were significantly higher in ITV plans at all levels tested. The median NTCP was 5.1% for RTT plans and 8.9% for ITV plans, with a median difference of 1.9% (range 0.4-25.5%, pairwise P < 0.001). Increases in NTCP between plans were best predicted by increases in PTV volume and PTV/lung volume ratio. CONCLUSIONS: The use of RTT decreased the risk of radiation pneumonitis in all plans. However, for most patients the risk reduction was minimal. Differences in plan PTV volume and PTV/lung volume ratio may identify patients who would benefit from RTT technique before completing treatment planning.

Major prognostic factors for recurrence and survival independent of the American Joint Committee on Cancer eighth edition staging system in patients with cutaneous squamous cell carcinoma treated with multimodality therapy.

BACKGROUND: The purpose of this study was to assess changes resulting from the American Joint Committee on Cancer (AJCC) eighth edition for cutaneous squamous cell carcinoma (SCC) and evaluate pertinent excluded factors. METHODS: In 101 patients receiving surgery and postoperative radiation, recurrence and survival were estimated by cumulative incidence and Kaplan-Meier method. Time-to-event analysis was performed using Cox proportional hazards and Fine-Gray competing risks regression models. RESULTS: The 2-year locoregional recurrence, overall survival (OS), and cause-specific mortality rates were 25%, 72%, and 13%, respectively. The AJCC eighth edition upstaged T classification in 50% of patients and overall stage in 39%. In multivariate analysis, immunosuppression and in-transit metastasis were associated with locoregional recurrence. Older age and in-transit metastasis were associated with worse OS. In univariate analysis (limited by number of events), cause-specific mortality was associated with positive margin, in-transit metastasis, and the seventh edition dichotomized T classification and overall stage. CONCLUSION: In-transit metastasis was significantly associated with locoregional recurrence, OS, and cause-specific mortality. Efforts should be made to define in-transit metastasis in the staging system.

Dural recurrence among esthesioneuroblastoma patients presenting with intracranial extension.

OBJECTIVE: To quantify the rate of late intracranial recurrences among esthesioneuroblastoma patients treated with surgical resection and postoperative radiation. STUDY DESIGN: Retrospective review. METHODS: All patients receiving definitive-intent therapy for esthesioneuroblastoma between March 1995 and September 2015 were reviewed. Presenting disease extent was categorized based on radiologic, operative, and pathologic findings. Between-group survival differences were assessed using Kaplan-Meier method and log-rank test. Multivariate analyses were performed using Cox proportional hazards model. RESULTS: Of 38 patients initially treated at our institution, 53% (20 of 38) presented with intracranial extension. At a median follow-up of 90 months (range, 6-199), 37% (14 of 38) recurred; 5- and 8-year disease-free survival rates were 69% and 54%; and overall survival rates were 81% and 72%, respectively. Among these patients, the dura was the most commonly involved site of relapse (8), followed by local (6), regional (5), and distant extracranial (3) sites; and five patients had ≥ two categories of failure. Eight-year dural disease-free survival was 57% versus 90% (P = 0.017) and 0% versus 87% (P < 0.0001), with and without intracranial extension and subtotal resection, respectively. Of six patients treated at recurrence, five (83%) experienced dural-based failure such that, among all 44 patients, 13 (65%) of 20 recurrences involved the dura. After dural recurrence, the median survival time was 42 months (range, 12-125); salvage treatments were effective in rare cases of isolated low-volume recurrence. CONCLUSION: Esthesioneuroblastoma patients presenting with intracranial extension are at substantial and unique risk for long-term dural-based relapse. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2226-2233, 2018.

Squamous cell carcinoma of unknown primary of the head and neck: Favorable prognostic factors comparable to those in oropharyngeal cancer.

BACKGROUND: Treatment for squamous cell carcinoma (SCC) of unknown primary consists of radiotherapy (RT) +/- chemotherapy or neck dissection +/- adjuvant RT/chemoradiotherapy (CRT). We compared these strategies and identified prognostic factors. METHODS: From 1993 to 2015, 75 patients with SCC of unknown primary had RT-based or surgery-based treatment. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Event-time distributions were estimated using the Kaplan-Meier method. RESULTS: Five-year OS and DFS for RT-based and surgery-based treatments were similar (OS 73% vs 68%, respectively; DFS 65% vs 64%, respectively). Among 38 patients with p16 data, 76% were p16 positive and showed improved 5-year DFS (90% vs 33%; P = .001) and OS (96% vs 33%; P < .001). Smoking history ≤10 pack-years conferred better 5-year DFS (88% vs 49%; P < .001) and OS (91% vs 59%; P < .001). CONCLUSION: RT-based and surgery-based treatments produced similar outcomes. Patients with p16-positive disease with ≤10 pack-years of smoking history and limited nodal stage constitute a "low-risk" group in SCC of unknown primary similar to that in oropharyngeal cancer.

Management of Chordoma and Chondrosarcoma with Fractionated Stereotactic Radiotherapy.

OBJECTIVE: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) for chordoma and chondrosarcoma. METHODS: Twenty consecutive patients with a histopathologic diagnosis of chordoma (n = 16) or chondrosarcoma (n = 4) treated between 2010 and 2016 were retrospectively identified. All patients underwent FSRT in five fractions to a median dose of 37.5 Gy (range: 25-40 Gy) and followed with serial magnetic resonance imaging. Overall survival (OS), local recurrence-free survival (LRFS), and event-free survival (EFS) were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 28 months after FSRT and 40 months after initial surgery, crude OS and LRFS were 90%. Nine patients (45%) reported grade 1-3 acute toxicity, and two patients (10%) experienced grade 4, 5 late toxicity. One patient previously treated with proton therapy died from radiation vasculopathy 9 months after FSRT. The use of FSRT for recurrent disease or in patients with prior radiation therapy was associated with significantly decreased EFS. CONCLUSION: FSRT for chordoma and chondrosarcoma is associated with high rates of OS and local control. Although many patients experience acute toxicity, there is a low incidence of late toxicity or irreversible treatment related morbidity despite the frequency of prior radiotherapy in this population. FSRT is an effective adjuvant or salvage treatment for chordoma and chondrosarcoma.

A multi-institutional comparison of outcomes of immunosuppressed and immunocompetent patients treated with surgery and radiation therapy for cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Patients who are chronically immunosuppressed have higher rates of cutaneous squamous cell carcinoma of the head and neck (cSCC-HN). This is the largest multi-institutional study to date investigating the effect of immune status on disease outcomes in patients with cSCC-HN who underwent surgery and received postoperative radiation therapy (RT). METHODS: Patients from 3 institutions who underwent surgery and also received postoperative RT for primary or recurrent, stage I through IV cSCC-HN between 1995 and 2015 were included in this institutional review board-approved study. Patients categorized as immunosuppressed had chronic hematologic malignancy, human immunodeficiency/acquired immunodeficiency syndrome, or had received immunosuppressive therapy for organ transplantation ≥6 months before diagnosis. Overall survival, locoregional recurrence-free survival, and progression-free survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional-hazards regression. RESULTS: Of 205 patients, 138 (67.3%) were immunocompetent, and 67 (32.7%) were immunosuppressed. Locoregional recurrence-free survival (47.3% vs 86.1%; P < .0001) and progression-free survival (38.7% vs 71.6%; P = .002) were significantly lower in immunosuppressed patients at 2 years. The 2-year OS rate in immunosuppressed patients demonstrated a similar trend (60.9% vs 78.1%; P = .135) but did not meet significance. On multivariate analysis, immunosuppressed status (hazard ratio [HR], 3.79; P < .0001), recurrent disease (HR, 2.67; P = .001), poor differentiation (HR, 2.08; P = .006), and perineural invasion (HR, 2.05; P = .009) were significantly associated with locoregional recurrence. CONCLUSIONS: Immunosuppressed patients with cSCC-HN had dramatically lower outcomes compared with immunocompetent patients, despite receiving bimodality therapy. Immune status is a strong prognostic factor that should be accounted for in prognostic systems, treatment algorithms, and clinical trial design. Cancer 2017;123:2054-2060. © 2017 American Cancer Society.

Does radiation dose matter in thyroid cancer?: Patterns of local-regional failure in recurrent and metastatic well-differentiated thyroid cancers treated with dose-painted intensity-modulated radiation therapy.

INTRODUCTION: Due to complex multimodal treatments and a lengthy natural history of disease, the impact of radiation therapy for well-differentiated thyroid cancer (WDTC) is challenging to evaluate. We analysed the effect of dose escalation, as enabled by intensity-modulated radiation therapy (IMRT), on preventing local-regional failure (LRF) of microscopic and macroscopic WDTC. METHOD: We performed a retrospective review of WDTC patients treated with IMRT from 1998-2011. Diagnostic imaging demonstrating first LRF was registered to the simulation CT containing the treated radiation isodose volumes. Areas of disease progression were contoured and the relationships of LRFs with isodose volumes were recorded. RESULTS: Thirty patients had a median follow-up of 56 months (range = 1-139). Seventeen (57%) had gross residual, five (17%) had microscopic residual and eight (27%) had clear margins at the time of IMRT. Nine patients (30%) developed LRF, at a median time of 44 months (range = 0-116). Of these, six (67%) had been radiated to gross disease and one (11%) had microscopic residual. In the seven analysable cases, only one (14%) LRF occurred within the 70 Gy isodose volume. Marginal LRFs were: four (57%) outside 70 Gy, one (14%) outside 60 Gy and one (14%) outside 50 Gy. All but one recurrence (86%) occurred in the perioesophageal region. CONCLUSIONS: Local-regional failure was seen most in patients who had gross disease at the time of IMRT, almost always occurred outside of the 70 Gy volume and was frequently in the area of oesophageal sparing. Meticulous surgical dissection, especially in the perioesophageal region, should be prioritised to prevent long-term LRF.

Transperineal ultrasound-guided implantation of electromagnetic transponders in the prostatic fossa for localization and tracking during external beam radiation therapy.

PURPOSE: To describe a transperineal ultrasound-guided technique for implantation of electromagnetic transponders into the prostatic fossa. METHODS AND MATERIALS: Patients were placed in the dorsal lithotomy position, and local anesthetic was administered. On ultrasound, the bladder, urethra, vesicourethral anastomosis, rectum, and the prostatic fossa were carefully identified. Three transponders were implanted into the prostatic fossa under ultrasound guidance in a triangular configuration and implantation was verified by fluoroscopy. Patients underwent computed tomography (CT) simulation approximately 1 week later. All patients in this study were subsequently treated with intensity modulated radiation therapy (IMRT) to the prostatic fossa. RESULTS: From 2008 to 2012, 180 patients received transperineal implantation of electromagnetic transponders into the prostatic fossa and subsequently received IMRT. There were no cases of severe hematuria or rectal bleeding requiring intervention. There were no grade 3 or 4 toxicities. Three patients (1.7%) had a transponder missing on the subsequent CT simulation. Thirteen patients (7.3%) had transponder migration with a geometric residual that exceeded 2 mm for 3 consecutive days (5.6%) or rotation that exceeded 10 degrees for 5 consecutive days (1.7%). These patients underwent a resimulation CT scan to identify the new transponder coordinates. CONCLUSIONS: A transperineal technique for implantation of electromagnetic transponders into the prostatic fossa is safe and well tolerated, with no severe toxicity after implantation. There is a low rate of transponder loss or migration.

Predictors of individual tumor local control after stereotactic radiosurgery for non-small cell lung cancer brain metastases.

PURPOSE: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. RESULTS: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥ 1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. CONCLUSIONS: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.

Outcomes of iodine-125 plaque brachytherapy for uveal melanoma with intraoperative ultrasonography and supplemental transpupillary thermotherapy.

PURPOSE: To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB). METHODS AND MATERIALS: Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method. RESULTS: The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02). CONCLUSIONS: Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions.

A prospective longitudinal clinical trial evaluating quality of life after breast-conserving surgery and high-dose-rate interstitial brachytherapy for early-stage breast cancer.

PURPOSE: To prospectively examine quality of life (QOL) of patients with early stage breast cancer treated with accelerated partial breast irradiation (APBI) using high-dose-rate (HDR) interstitial brachytherapy. METHODS AND MATERIALS: Between March 2004 and December 2008, 151 patients with early stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients included those with Tis-T2 tumors measuring ≤3 cm excised with negative surgical margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. QOL was measured using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, version 3.0, and QLQ-BR23 questionnaires. The QLQ-C30 and QLQ-BR23 questionnaires were evaluated during pretreatment and then at 6 to 8 weeks, 3 to 4 months, 6 to 8 months, and 1 and 2 years after treatment. RESULTS: The median follow-up was 55 months. Breast symptom scores remained stable in the months after treatment, and they significantly improved 6 to 8 months after treatment. Scores for emotional functioning, social functioning, and future perspective showed significant improvement 2 years after treatment. Symptomatic fat necrosis was associated with several changes in QOL, including increased pain, breast symptoms, systemic treatment side effects, dyspnea, and fatigue, as well as decreased role functioning, emotional functioning, and social functioning. CONCLUSIONS: HDR multicatheter interstitial brachytherapy was well tolerated, with no significant detrimental effect on measured QOL scales/items through 2 years of follow-up. Compared to pretreatment scores, there was improvement in breast symptoms, emotional functioning, social functioning, and future perspective 2 years after treatment.

Stereotactic body radiation therapy for the treatment of early-stage minimally invasive adenocarcinoma or adenocarcnioma in situ (formerly bronchioloalveolar carcinoma): a patterns of failure analysis.

INTRODUCTION: Ongoing prospective trials exploring stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) often exclude minimally invasive adenocarcinoma or adenocarcnioma in situ, formerly bronchioloalveolar carcinoma (BAC), due to concerns for accurate target delineation on CT. We performed a patterns of failure analysis to compare outcomes between BAC and other NSCLC subtypes. METHODS: One hundred twenty patients with early stage NSCLC were treated with SBRT from 2004-2009. Pathologic confirmation of NSCLC was obtained in 97 patients. Radiotherapy was delivered according to RTOG guidelines. The log-rank test was used to compare outcomes between BAC and other NSCLC. RESULTS: Median follow-up was 29 months. The median SBRT dose was 5400 cGy. Thirteen patients had radiographically diagnosed BAC and five patients had biopsy confirmed BAC, of which two had both. The three-year local control was 100% for biopsy-proven or radiographically diagnosed BAC (n = 18) and 86% for all other NSCLC subtypes (n = 102) (p = 0.13). Likewise, no significant difference was detected between BAC and other NSCLC for 3-year regional failure (12% vs. 20%, p = 0.45), progression-free survival (57.6% vs. 53.5%, p = 0.84) or overall survival (35% vs. 47%, p = 0.66). There was a trend towards lower three-year rates of freedom from distant failure in patients with any diagnosis of BAC compared to those without (26% vs. 38%, p = 0.053). CONCLUSIONS: Compared to other NSCLC subtypes, BAC appears to have similar patterns of failure and survival after treatment with SBRT, however there may be an increased risk of distant metastases with BAC. RTOG guideline-based target delineation provides encouraging local control rates for patients with BAC.

Analysis of fat necrosis after adjuvant high-dose-rate interstitial brachytherapy for early stage breast cancer.

PURPOSE: To report the incidence and potential predictors of fat necrosis in women with early stage breast cancer treated with adjuvant high-dose-rate (HDR) multicatheter interstitial brachytherapy. METHODS AND MATERIALS: Between 2003 and 2010, 238 treated breasts in 236 women were treated with accelerated partial breast irradiation using HDR interstitial brachytherapy. Selection criteria included patients with Tis-T2 tumors measuring ≤3cm, without nodal involvement, who underwent breast-conserving surgery. Ninety-nine percent of treatments were to a total dose of 34Gy. The presence and severity of fat necrosis were prospectively recorded during followup. Cosmesis was qualitatively scored in all patients. Cosmesis was quantitatively measured via the percentage breast retraction assessment in 151 cases. RESULTS: Median followup was 56 months. The crude rate of fat necrosis was 17.6%. The rate of symptomatic fat necrosis was 10.1%. In univariate analysis, acute breast infection and anthracycline-based chemotherapy, number of catheters, volume encompassed by the prescription isodose, volume encompassed by the 150% isodose (V150), volume encompassed by the 200% isodose, and integrated reference air kerma were significantly associated with fat necrosis. There was significant collinearity between the brachytherapy-related factors; of these, V150 was most predictive. In multivariate analysis, only V150 was significantly associated with fat necrosis. At 3 years, patients with fat necrosis were more likely to have a fair or poor cosmetic outcome and a larger percentage breast retraction assessment. CONCLUSIONS: Mammary fat necrosis is a common adverse event after breast-conserving surgery and HDR interstitial brachytherapy. Fat necrosis is associated with worse qualitative and quantitative cosmetic outcomes. Minimizing exposure volumes, such as V150, may decrease the incidence of fat necrosis and improve cosmesis.

Cosmetic analysis following breast-conserving surgery and adjuvant high-dose-rate interstitial brachytherapy for early-stage breast cancer: a prospective clinical study.

PURPOSE: To prospectively evaluate cosmetic outcomes in women treated with accelerated partial breast irradiation using high-dose-rate interstitial brachytherapy for early-stage breast cancer. METHODS AND MATERIALS: Between 2004 and 2008, 151 patients with early-stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients had stage Tis-T2 tumors of ≤3 cm that were excised with negative margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. Both the patients and the treating radiation oncologist qualitatively rated cosmesis as excellent, good, fair, or poor over time and ascribed a cause for changes in cosmesis. Cosmetic outcome was evaluated quantitatively by percentage of breast retraction assessment (pBRA). Patients also reported their satisfaction with treatment over time. RESULTS: Median follow-up was 55 months. The rates of excellent-to-good cosmesis reported by patients and the treating radiation oncologist were 92% and 97% pretreatment, 91% and 97% at 3 to 4 months' follow-up, 87% and 94% at 2 years, and 92% and 94% at 3 years, respectively. Breast infection and adjuvant chemotherapy were independent predictors of a fair-to-poor cosmetic outcome at 3 years. Compared to pretreatment pBRA (7.35), there was no significant change in pBRA over time. The volume receiving more than 150 Gy (V150) was the only significant predictor of pBRA. The majority of patients (86.6%) were completely satisfied with their treatment. CONCLUSIONS: Patients and the treating physician reported a high rate of excellent-to-good cosmetic outcomes at all follow-up time points. Acute breast infection and chemotherapy were associated with worse cosmetic outcomes. Multicatheter interstitial brachytherapy does not significantly change breast size as measured by pBRA.

Prognostic value of 18F-FDG PET metabolic parameters in oropharyngeal squamous cell carcinoma.

OBJECTIVE: To evaluate whether pretreatment metabolic parameters obtained from positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) can improve risk prediction for patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive intensity-modulated radiation therapy (IMRT). METHODS: Between 2003 and 2009, 86 patients with OPSCC had FDG-PET/CT prior to treatment with definitive IMRT. Chemotherapy was administered to 90 % of the patients. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax), mean SUV (SUVmean), and inverse coefficient of variation (1/CoV) were analyzed for the primary tumor alone and the total of the primary tumor and involved lymph nodes. RESULTS: Median follow-up time for surviving patients was 41 months. On univariate analysis, total MTV and total TLG were significant predictors of disease-free survival (DFS) and overall survival (OS). SUVmax, SUVmean, and 1/CoV failed to predict DFS or OS. On multivariate analysis controlling for T- and N-classification, total MTV remained a significant predictor of DFS and OS. The optimal cutpoint for total MTV was 20.5 ml. A total MTV >20.5 ml was associated with a 4.13-fold increased risk of death (95 % confidence interval [CI], 2.12-8.05; p < 0.0001). Total MTV remained a significant predictor of DFS and OS for the subgroups with p16-positive (n = 25) and p16-negative (n = 18) cancer. CONCLUSION: Total MTV is an independent predictor of DFS and OS for patients with OPSCC treated with definitive radiotherapy. Total MTV remained predictive of DFS and OS for both p16-positive and p16-negative cancer.

Comparison of accelerated partial breast irradiation via multicatheter interstitial brachytherapy versus whole breast radiation.

BACKGROUND: Brachytherapy as adjuvant treatment for early-stage breast cancer has become widely available and offers patients an expedited treatment schedule. Given this, many women are electing to undergo brachytherapy in lieu of standard fractionation radiotherapy. We compare outcomes between patients treated with accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy versus patients who were also eligible for and offered APBI but who chose whole breast radiation (WBI). METHODS: Patients treated from December 2002 through May 2007 were reviewed. Selection criteria included patients with pTis-T2N0 disease, ≤ 3 cm unifocal tumors, and negative margins who underwent breast conservation surgery. Local control (LC), cause-specific (CSS) and overall survival (OS) were analyzed. RESULTS: 202 patients were identified in the APBI cohort and 94 patients in the WBI cohort. Median follow-up for both groups exceeded 60 months. LC was 97.0% for the APBI cohort and 96.2% for the WBI cohort at 5 years (ns). Classification by 2010 ASTRO APBI consensus statement categories did not predict worse outcomes. CONCLUSION: APBI via multicatheter interstitial brachytherapy provides similar local failure rates compared to WBI at 5 years for properly selected patients. Excellent results were seen despite the high fraction of younger patients (< 60 years old) and patients with DCIS.

Pyrosequencing of clinically relevant polymorphisms.

The data generated from the Human Genome Project has led to an explosion of technology for low-, medium-, and high-throughput genotyping methods. Pyrosequencing is a genotyping assay based on sequencing by synthesis. Short runs of sequence around each polymorphism are generated, allowing for internal controls for each sample. Pyrosequencing can also be used to identify tri-allelic, indel, and short-repeat polymorphisms, as well as determining allele percentages for methylation or pooled sample assessment. Assays details for Pyrosequencing of clinically relevant polymorphisms are described in this chapter.

CYP3A4 and CYP3A5 genotyping by Pyrosequencing.

BACKGROUND: Human cytochrome P450 3A enzymes, particularly CYP3A4 and CYP3A5, play an important role in drug metabolism. CYP3A expression exhibits substantial interindividual variation, much of which may result from genetic variation. This study describes Pyrosequencing assays for key SNPs in CYP3A4 (CYP3A4*1B, CYP3A4*2, and CYP3A4*3) and CYP3A5 (CYP3A5*3C and CYP3A5*6). METHODS: Genotyping of 95 healthy European and 95 healthy African volunteers was performed using Pyrosequencing. Linkage disequilibrium, haplotype inference, Hardy-Weinberg equilibrium, and tag SNPs were also determined for these samples. RESULTS: CYP3A4*1B allele frequencies were 4% in Europeans and 82% in Africans. The CYP3A4*2 allele was found in neither population sample. CYP3A4*3 had an allele frequency of 2% in Europeans and 0% in Africans. The frequency of CYP3A5*3C was 94% in Europeans and 12% in Africans. No CYP3A5*6 variants were found in the European samples, but this allele had a frequency of 16% in the African samples. Allele frequencies and haplotypes show interethnic variation, highlighting the need to analyze clinically relevant SNPs and haplotypes in a variety of ethnic groups. CONCLUSION: Pyrosequencing is a versatile technique that could improve the efficiency of SNP analysis for pharmacogenomic research with the ultimate goal of pre-screening patients for individual therapy selection.