Multiparametric MRI as a Predictor of PSA Response in Patients Undergoing Stereotactic Body Radiation Therapy for Prostate Cancer.

Purpose: To maximize the therapeutic ratio, it is important to identify adverse prognostic features in men with prostate cancer, especially among those with intermediate risk disease, which represents a heterogeneous group. These men may benefit from treatment intensification. Prior studies have shown pretreatment mpMRI may predict biochemical failure in patients with intermediate and/or high-risk prostate cancer undergoing conventionally fractionated external beam radiation therapy and/or brachytherapy. This study aims to evaluate pretreatment mpMRI findings as a marker for outcome in patients undergoing stereotactic body radiation therapy (SBRT). Methods and Materials: We identified all patients treated at our institution with linear accelerator based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) from November 2015 to March 2021. All patients underwent pretreatment Magnetic Resonance Imaging (MRI). Posttreatment Prostate Specific Imaging (PSA) measurements were typically obtained 4 months after SBRT, followed by every 3 to 6 months thereafter. A 2 sample t test was used to compare preoperative mpMRI features with clinical outcomes. Results: One hundred twenty-three men were included in the study. Pretreatment MRI variables including median diameter of the largest intraprostatic lesion, median number of prostate lesions, and median maximal PI-RADS score, were each predictive of PSA nadir and time to PSA nadir (P < .0001). When separated by ADT treatment, this association remained for patients who were not treated with ADT (P < .001). In patients who received ADT, the pretreatment MRI variables were each significantly associated with time to PSA nadir (P < .01) but not with PSA nadir (P > 0.30). With a median follow-up time of 15.9 months (IQR: 8.5-23.3), only 3 patients (2.4%) experienced biochemical recurrence as defined by the Phoenix criteria. Conclusions: Our experience shows the significant ability of mpMRI for predicting PSA outcome in prostate cancer patients treated with SBRT with or without ADT. Since PSA nadir has been shown to correlate with biochemical failure, this information may help radiation oncologists better counsel their patients regarding outcome after SBRT and can help inform future studies regarding who may benefit from treatment intensification with, for example, ADT and/or boosts to dominant intraprostatic lesions.

A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study.

BACKGROUND: Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients. OBJECTIVE: To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT). DESIGN, SETTING, AND PARTICIPANTS: A multicenter phase 1 trial was conducted at community and academic sites. INTERVENTION: Patients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy × 3 in cycle 1 only). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-treatment cystoscopy and urine cytology were performed at 3 and 6 -mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates. RESULTS AND LIMITATIONS: Twenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions × 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients. CONCLUSIONS: D combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches. PATIENT SUMMARY: Durvalumab combination therapy can be safely administered to non-muscle-invasive bladder cancer patients with the goal of increasing durable response rates.

Telemedicine in management of genitourinary malignancies: Patient and physician perspectives.

PURPOSE: The rapid expansion of telemedicine has presented a challenge for the care of patients with genitourinary malignancies. We sought to assess patient and physician perspectives on the use of telemedicine for genitourinary cancer care. METHODS: We conducted a prospective cross-sectional study of patients who had telemedicine visits with urology, medical oncology, or radiation oncology for management of genitourinary malignancies from July-August 2020. Patients and physicians each received a questionnaire regarding the telemedicine experience. Responses were scored on a 5-point Likert scale. The primary outcomes of the study were patient and physician satisfaction. RESULTS: Of the 115 patients who enrolled, we received 96 patient responses and 46 physician responses. Overall, 77% of patients and 70% of physicians reported being "extremely satisfied" with the telemedicine encounter. Satisfaction was high among all components of the encounter including patient-physician communication, counseling, shared decision making, time spent, timeliness and efficiency, and convenience. Additionally, 78% of patients and 85% of physicians "strongly agreed" that they were able to discuss sensitive topics about cancer care as well as they could at an in-person visit. Nine telemedicine visits (9%) encountered technological barriers. Technological barriers were associated with lower overall satisfaction scores among both patients and physicians (p ≤ 0.01). CONCLUSION: We observed high levels of patient and physician satisfaction for telemedicine visits for management of genitourinary malignancies. Technological barriers were encountered by 9% of patients and were associated with decreased satisfaction.

Dosimetric feasibility of neurovascular bundle-sparing stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer to preserve erectile function.

OBJECTIVE: We aim to test the hypothesis that neurovascular bundle (NVB) displacement by rectal hydrogel spacer combined with NVB delineation as an organ at risk (OAR) is a feasible method for NVB-sparing stereotactic body radiotherapy. METHODS: Thirty-five men with low- and intermediate-risk prostate cancer who underwent rectal hydrogel spacer placement and pre-, post-spacer prostate MRI studies were treated with prostate SBRT (36.25 Gy in five fractions). A prostate radiologist contoured the NVB on both the pre- and post-spacer T2W MRI sequences that were then registered to the CT simulation scan for NVB-sparing radiation treatment planning. Three SBRT treatment plans were developed for each patient: (1) no NVB sparing, (2) NVB-sparing using pre-spacer MRI, and (3) NVB-sparing using post-spacer MRI. NVB dose constraints include maximum dose 36.25 Gy (100%), V34.4 Gy (95% of dose) <60%, V32Gy <70%, V28Gy <90%. RESULTS: Rectal hydrogel spacer placement shifted NVB contours an average of 3.1 ± 3.4 mm away from the prostate, resulting in a 10% decrease in NVB V34.4 Gy in non-NVB-sparing plans (p < 0.01). NVB-sparing treatment planning reduced the NVB V34.4 by 16% without the spacer (p < 0.01) and 25% with spacer (p < 0.001). NVB-sparing did not compromise PTV coverage and OAR endpoints. CONCLUSIONS: NVB-sparing SBRT with rectal hydrogel spacer significantly reduces the volume of NVB treated with high-dose radiation. Rectal spacer contributes to this effect through a dosimetrically meaningful displacement of the NVB that may significantly reduce RiED. These results suggest that NVB-sparing SBRT warrants further clinical evaluation. ADVANCES IN KNOWLEDGE: This is a feasibility study showing that the periprostatic NVBs can be spared high doses of radiation during prostate SBRT using a hydrogel spacer and nerve-sparing treatment planning.

Primary Episcleral Melanoma Consistent with Uveal Melanoma Mutations Treated by Excision and Gamma Knife Stereotactic Radiosurgery.

Ocular melanocytosis has traditionally been associated with increased risk of developing uveal melanoma; however, rarely primary episcleral melanoma has been reported in the literature. Herein, we present the third case of primary episcleral melanoma treated by complete excision and cryotherapy. In contrast to previous cases, we obtained molecular genetic testing which revealed a GNA-11 mutation, and gene expression profiling resulted in a Class 2 PRAME positive tumor diagnosis. These two tests which have never been performed on previous cases, support lineage similar to uveal melanoma. In addition, we are the first case to report treatment of the surgical bed and surrounding orbital tissue with Gamma Knife stereotactic radiotherapy to both treat residual tissue and decrease risk of recurrence.

Clear Cell Adenocarcinoma of the Urinary Bladder Is a Glycogen-Rich Tumor with Poorer Prognosis.

Clear cell adenocarcinoma (CCA) is a rare variant of urinary bladder carcinoma with a glycogen-rich phenotype and unknown prognosis. Using the National Cancer Institute's surveillance, epidemiology, and end results (SEER) program database, we documented recent trends in incidence, mortality, demographical characteristics, and survival on this rare subtype of urinary bladder cancer. The overall age-adjusted incidence and mortality of CCA was 0.087 (95% confidence interval (CI): 0.069-0.107) and 0.064 (95% CI: 0.049-0.081) respectively per million population. In comparison to non-CCAs, CCAs were more commonly associated with younger age (<60 years old, p = 0.005), female (p < 0.001), black ethnicity (p = 0.001), grade III (p < 0.001), and higher AJCC 6th staging (p < 0.001). In addition, CCA patients more frequently received complete cystectomy (p < 0.001) and beam radiation (p < 0.001) than non-CCA patients. Our study showed a poorer prognosis of CCAs compared to all other carcinomas of the urinary bladder (p < 0.001), accounted for by higher tumor staging of CCA cases. This study adds to the growing evidence that glycogen-rich cancers may have unique characteristics affecting tumor aggressiveness and patient prognosis. Additional mechanistic studies are needed to assess whether it's the excess glycogen that contributes to the higher stage at diagnosis.

Stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer: toxicity profile and early oncologic outcomes.

BACKGROUND: Multiple phase I-II clinical trials have reported on the efficacy and safety of prostate stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer. However, few have reported outcomes for prostate SBRT using periprostatic hydrogel spacer (SpaceOAR; Augmenix). Herein, we report safety and efficacy outcomes from our institutional prostate SBRT experience with SpaceOAR placement. METHODS: Fifty men with low- or intermediate-risk prostate cancer treated at a single institution with linear accelerator-based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) were included. All patients underwent SpaceOAR and fiducial marker placement followed by pre-treatment MRI. Toxicity assessments were conducted at least weekly while on treatment, 1 month after treatment, and every follow-up visit thereafter. Post-treatment PSA measurements were obtained 4 months after SBRT, followed by every 3-6 months thereafter. Acute toxicity was documented per RTOG criteria. RESULTS: Median follow up time was 20 (range 4-44) months. Median PSA at time of diagnosis was 7.4 (2.7-19.5) ng/ml. Eighteen men received 6 months of ADT for unfavorable intermediate risk disease. No PSA failures were recorded. Median PSA was 0.9 ng/mL at 20 months; 0.08 and 1.32 ng/mL in men who did and did not receive ADT, respectively. Mean prostate-rectum separation achieved with SpaceOAR was 9.6 ± 4 mm at the prostate midgland. No grade ≥ 3 GU or GI toxicity was recorded. During treatment, 30% of men developed new grade 2 GU toxicity (urgency or dysuria). These symptoms were present in 30% of men at 1 month and in 12% of men at 1 year post-treatment. During treatment, GI toxicity was limited to grade 1 symptoms (16%), although 4% of men developed grade 2 symptoms during the first 4 weeks after SBRT. All GI symptoms were resolving by the 1 month post-treatment assessment and no acute or late rectal toxicity was reported > 1 month after treatment. CONCLUSIONS: Periprostatic hydrogel placement followed by prostate SBRT resulted in minimal GI toxicity, and favorable early oncologic outcomes. These results indicate that SBRT with periprostatic spacer is a well-tolerated, safe, and convenient treatment option for localized prostate cancer.

Patterns of care and outcomes for women with uterine cancer and ovarian metastases.

OBJECTIVE: For women with uterine cancer with metastases isolated to the adnexa (stage IIIA) optimal adjuvant therapy is unknown. We performed a population-based analysis to examine the use of chemotherapy, vaginal brachytherapy, and external beam therapy (in women with stage IIIA uterine cancer. METHODS: The National Cancer Database was used to identify women with stage IIIA uterine cancer with ovarian metastasis from 2004 to 2012. We explored the use of chemotherapy, vaginal brachytherapy, and external beam therapy over time. Multivariable models were developed to examine factors associated with survival. RESULTS: We identified 4088 women with uterine cancer and ovarian metastases. Overall, 56.2% of women received chemotherapy. Vaginal brachytherapy was used in 11.1%, while 36.6% received external beam therapy. Five-year survival was 64.7 % (95% CI, 62.9% to 66.5%). In a multivariable model, chemotherapy was associated with a 38% decrease in mortality (HR = 0.62; 95% CI, 0.54 to 0.71). Similarly, both external beam therapy (HR = 0.74; 95% CI, 0.65 to 0.85) and vaginal brachytherapy (HR = 0.67; 95% CI, 0.53 to 0.85) were associated with improved survival. When the cohort was limited to women who received chemotherapy, radiation was associated with improved overall survival (HR 0.74, 95% CI 0.61 to 0.90). There was no difference in survival between the use of external beam therapy and vaginal brachytherapy. CONCLUSIONS: Chemotherapy was associated with a decrease in mortality in women with endometrial cancer and ovarian metastases. The addition of radiation therapy was associated with improved overall survival, although there was no difference between external beam therapy and vaginal brachytherapy.

A novel model to correlate hydrogel spacer placement, perirectal space creation, and rectum dosimetry in prostate stereotactic body radiotherapy.

BACKGROUND: The SpaceOAR hydrogel is employed to limit rectal radiation dose during prostate radiotherapy. We identified a novel parameter - the product of angle θ and hydrogel volume - to quantify hydrogel placement. This parameter predicted rectum dosimetry and acute rectal toxicity in prostate cancer patients treated with stereotactic body radiotherapy to 36.25 Gy in 5 fractions. METHODS: Twenty men with low- and intermediate-risk prostate cancer underwent hydrogel placement from 2015 to 2017. Hydrogel symmetry was assessed on the CT simulation scan in 3 axial slices (midgland, 1 cm above midgland, 1 cm below midgland). Two novel parameters quantifying hydrogel placement - hydrogel volume and angle θ formed by the prostate, hydrogel, and rectum - were measured, and the normalized product of θ and hydrogel volume calculated. These were then correlated with perirectal distance, rectum maximum 1-3 cc point doses (rDmax 1-3 cc), and rectum volumes receiving 80-95% of the prescription dose (rV80-95%). Acute rectal toxicity was recorded per RTOG criteria. RESULTS: In 50% of patients, hydrogel placement was symmetric bilaterally to within 1 cm of midline in all three CT simulation scan axial slices. Lateral hydrogel asymmetry < 2 cm in any one axial slice did not affect rectum dosimetry, but absence of hydrogel in the inferior axial slice resulted in a mean increase of 171 cGy in the rDmax 1 cc (p < 0.005). The perirectal distance measured at prostate midgland, midline (mean 9.1 ± 4.3 mm) correlated strongly with rV95 (R2 0.6, p < 0.001). The mean hydrogel volume and θ were 10.3 ± 4.5 cc and 70 ± 49°, respectively. Perirectal distance, rV95 and rDmax 1 cc correlated with hydrogel angle θ (p < 0.01), and yet more strongly with the novel metric θ*hydrogel volume (p < 0.001). With a median follow up of 14 months, no rectal toxicity >grade 2 was observed. Low grade rectal toxicity was observed in a third of men and resolved within 1 month of SBRT. Men who had these symptoms had higher rDmax 1 cc and smaller θ*hydrogel volume measurements. CONCLUSIONS: Optimal hydrogel placement occurs at prostate midgland, midline. The novel parameter θ*hydrogel volume describes a large proportion of rectum dosimetric benefit derived from hydrogel placement, and can be used to assess the learning curve phenomenon for hydrogel placement.

Rectal balloon use limits vaginal displacement, rectal dose, and rectal toxicity in patients receiving IMRT for postoperative gynecological malignancies.

Pelvic radiotherapy for gynecologic malignancies traditionally used a 4-field box technique. Later trials have shown the feasibility of using intensity-modulated radiotherapy (IMRT) instead. But vaginal movement between fractions is concerning when using IMRT due to greater conformality of the isodose curves to the target and the resulting possibility of missing the target while the vagina is displaced. In this study, we showed that the use of a rectal balloon during treatment can decrease vaginal displacement, limit rectal dose, and limit acute and late toxicities. Little is known regarding the use of a rectal balloon (RB) in treating patients with IMRT in the posthysterectomy setting. We hypothesize that the use of an RB during treatment can limit rectal dose and acute and long-term toxicities, as well as decrease vaginal cuff displacement between fractions. We performed a retrospective review of patients with gynecological malignancies who received postoperative IMRT with the use of an RB from January 1, 2012 to January 1, 2015. Rectal dose constraint was examined as per Radiation Therapy Oncology Group (RTOG) 1203 and 0418. Daily cone beam computed tomography (CT) was performed, and the average (avg) displacement, avg magnitude, and avg magnitude of vector were calculated. Toxicity was reported according to RTOG acute radiation morbidity scoring criteria. Acute toxicity was defined as less than 90 days from the end of radiation treatment. Late toxicity was defined as at least 90 days after completing radiation. Twenty-eight patients with postoperative IMRT with the use of an RB were examined and 23 treatment plans were reviewed. The avg rectal V40 was 39.3% ± 9.0%. V30 was65.1% ± 10.0%. V50 was 0%. Separate cone beam computed tomography (CBCT) images (n = 663) were reviewed. The avg displacement was as follows: superior 0.4 + 2.99 mm, left 0.23 ± 4.97 mm, and anterior 0.16 ± 5.18 mm. The avg magnitude of displacement was superior/inferior 2.22 ± 2.04 mm, laterally 3.41 ± 3.62 mm, and anterior/posterior 3.86 ± 3.45 mm. The avg vector magnitude was 6.60 ± 4.14 mm. For acute gastrointestinal (GI) toxicities, 50% experienced grade 1 toxicities and 18% grade 2 GI toxicities. For acute genitourinary (GU) toxicities, 21% had grade 1 and 18% had grade 2 toxicities. For late GU toxicities, 7% had grade 1 and 4% had grade 2 toxicities. RB for gynecological patients receiving IMRT in the postoperative setting can limit V40 rectal dose and vaginal displacement. Although V30 constraints were not met, patients had limited acute and late toxicities. Further studies are needed to validate these findings.

Utility of radiation therapy for early-stage uterine papillary serous carcinoma.

OBJECTIVE: Early-stage uterine papillary serous carcinoma (UPSC) has a poor prognosis and high recurrence rate. While adjuvant chemotherapy is generally recommended, the role of radiation is uncertain. We examined the association between vaginal brachytherapy and whole pelvic radiation and survival in women treated with and without adjuvant chemotherapy. METHODS: The National Cancer Data Base was used to identify women with stage I-II UPSC treated between 1998 and 2012. Trends in use of chemotherapy, brachytherapy, and external beam radiation over time were examined. The association between these treatments and mortality were examined using multivariable Cox proportional hazards models. RESULTS: A total of 7325 patients were identified. Overall, 2779 (37.9%) received chemotherapy. The use of vaginal brachytherapy increased from 7.2% in 1998 to 29.1% in 2012 (P<0.0001), while use of external beam radiation decreased from 18.2% to 11.7% over the same period (P<0.0001). Use of chemotherapy was associated with a 22% reduction in mortality (HR=0.78; 95% CI, 0.69-0.88). While brachytherapy was associated with decreased mortality (HR=0.67; 95% CI, 0.57-0.78), use of external beam radiation was not associated with survival (HR=1.03; 95% CI, 0.92-1.17). Stratified by stage, use of chemotherapy was associated with decreased mortality for women with stage IB and II tumors, but not for stage IA neoplasms. Vaginal brachytherapy was associated with reduced mortality for stage IA and II neoplasms. CONCLUSION: For women with early-stage UPSC, chemotherapy is associated with improved survival. Vaginal brachytherapy was also associated with improved survival, however, there was little benefit to use of external beam radiation.

De-escalation of radiation dose for human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma: A case report and preclinical and clinical literature review.

Traditionally, head and neck squamous cell carcinoma (HNSCC) has been considered to be a relatively homogeneous disease. However, recent data have demonstrated that human papillomavirus (HPV)-positive and HPV-negative disease are two different clinical entities associated with different outcomes. Preclinical and clinical studies have reported a divergence in treatment strategies as well as prognostic outcomes for HNSCCs that are HPV-positive versus HPV-negative. The present study describes the case of a 52-year-old man who presented with stage IVB cT2N3M0 right tonsillar HPV-positive squamous cell carcinoma. Induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF), followed by chemoradiation therapy with carboplatin and 70 Gray (Gy) radiation in daily fractions was recommended. The patient completed the TPF and carboplatin treatment; however, he was unable to tolerate the radiation course, receiving a final dose of 46 Gy. A 60-day follow-up right neck salvage dissection was subsequently performed. Despite having received a partial radiation treatment of 46 Gy, the patient had no pathological evidence of disease at 60 days post radiation treatment. Repeat positron emission tomography-computed tomography at 32 months after the right neck dissection revealed no evidence of disease. The present study also discusses the current preclinical in vitro and in vivo targets for HPV-positive HNSCC and the obstacles presented in advancing clinical treatment modalities. Previous preclinical models investigating radiation sensitivity have yielded mixed results. Thus, it is important to understand and establish representative preclinical models for studying HPV and HNSCC to improve clinical research and therapeutic development. This review may guide future understanding of the role of HPV in HNSCC.

Influence of treatment center and hospital volume on survival for locally advanced cervical cancer.

OBJECTIVE: Procedural volume is associated with outcomes for many surgical interventions. Little is known about the association between volume and outcomes of radiation. We examined the association between treatment center and hospital volume and outcomes for women with locally advanced cervical cancer treated with radiation. METHODS: Women with stage IIB-IVA cervical cancer treated with primary radiation from 1998 to 2011 and recorded in the National Cancer Database were examined. Hospital volume was estimated as the mean annualized volume, while center-specific effects on care were examined using a hospital-specific random effect. Multivariable regression models adjusted for metrics of treatment quality were used to estimate survival. RESULTS: 20,766 patients treated at 1115 hospitals were identified. The median follow-up was 24.2months while 5-year survival was 36.5% (95% CI, 35.6-37.4%). Higher hospital volume was associated with receipt of brachytherapy (P<0.05), but had no effect on use of chemotherapy. In a multivariable model accounting for clinical and demographic factors as well as quality of care, hospital volume was not associated with survival (P=0.25). The specific hospital in which patients received care was the strongest predictor of survival (P<0.0001) followed by stage, year of diagnosis and treatment quality (P<0.0001 for all). The hospital-specific effect on mortality expressed as a hazard ratio, ranged from 0.66 to 1.53 across hospitals. CONCLUSION: For locally advanced cervical cancer, hospital volume has a minimal impact on outcome; however, the specific center in which care is delivered is strongly associated with survival.

High versus low-dose rate brachytherapy for cervical cancer.

OBJECTIVES: Brachytherapy plays an important role in the treatment of cervical cancer. While small trials have shown comparable survival outcomes between high (HDR) and low-dose rate (LDR) brachytherapy, little data is available in the US. We examined the utilization of HDR brachytherapy and analyzed the impact of type of brachytherapy on survival for cervical cancer. METHODS: Women with stages IB2-IVA cervical cancer treated with primary (external beam and brachytherapy) radiotherapy between 2003-2011 and recorded in the National Cancer Database (NCDB) were analyzed. Generalized linear mixed models and Cox proportional hazards regression were used to examine predictors of HDR brachytherapy use and the association between HDR use and survival. RESULTS: A total of 10,564 women including 2681 (25.4%) who received LDR and 7883 (74.6%) that received HDR were identified. Use of HDR increased from 50.2% in 2003 to 83.9% in 2011 (P<0.0001). In a multivariable model, year of diagnosis was the strongest predictor of use of HDR. While patients in the Northeast were more likely to receive HDR therapy, there were no other clinical or socioeconomic characteristics associated with receipt of HDR. In a multivariable Cox model, survival was similar between the HDR and LDR groups (HR=0.93; 95% CI 0.83-1.03). Similar findings were noted in analyses stratified by stage and histology. Kaplan-Meier analyses demonstrated no difference in survival based on type of brachytherapy for stage IIB (P=0.68), IIIB (P=0.17), or IVA (P=0.16) tumors. CONCLUSIONS: The use of HDR therapy has increased rapidly. Overall survival is similar for LDR and HDR brachytherapy.

Detection of endobronchial intubation by monitoring the CO2 level above the endotracheal cuff.

Early detection of accidental endobronchial intubation (EBI) is still an unsolved problem in anesthesia and critical care daily practice. The aim of this study was to evaluate the ability of monitoring above cuff CO2 to detect EBI (the working hypothesis was that the origin of CO2 is from the unventilated, but still perfused, lung). Six goats were intubated under general anesthesia and the ETT positioning was verified by a flexible bronchoscope. The AnapnoGuard system, already successfully used to detect air leak around the ETT cuff, was used for continuous monitoring of above-the-cuff CO2 level. When the ETT distal tip was located in the trachea, with an average cuff pressure of 15 mmHg, absence of CO2 above the cuff was observed. The ETT was then deliberately advanced into one of the main bronchi under flexible bronchoscopic vision. In all six cases the immediate presence of CO2 above the cuff was identified. Further automatic inflation of the cuff, up to a level of 27 mmHg, did not affect the above-the-cuff measured CO2 level. Withdrawal of the ETT and repositioning of its distal tip in mid-trachea caused the disappearance of CO2 above the cuff in a maximum of 3 min, confirming the absence of air leak and the correct positioning of the ETT. Our results suggest that measurement of the above-the-cuff CO2 level could offer a reliable, on-line solution for early identification of accidental EBI. Further studies are planned to validate the efficacy of the method in a clinical setup.

Initial clinical experience performing patient treatment verification with an electronic portal imaging device transit dosimeter.

PURPOSE: To prospectively evaluate a 2-dimensional transit dosimetry algorithm's performance on a patient population and to analyze the issues that would arise in a widespread clinical adoption of transit electronic portal imaging device (EPID) dosimetry. METHODS AND MATERIALS: Eleven patients were enrolled on the protocol; 9 completed and were analyzed. Pretreatment intensity modulated radiation therapy (IMRT) patient-specific quality assurance was performed using a stringent local 3%, 3-mm γ criterion to verify that the planned fluence had been appropriately transferred to and delivered by the linear accelerator. Transit dosimetric EPID images were then acquired during treatment and compared offline with predicted transit images using a global 5%, 3-mm γ criterion. RESULTS: There were 288 transit images analyzed. The overall γ pass rate was 89.1%±9.8% (average±1 SD). For the subset of images for which the linear accelerator couch did not interfere with the measurement, the γ pass rate was 95.7%±2.4%. A case study is presented in which the transit dosimetry algorithm was able to identify that a lung patient's bilateral pleural effusion had resolved in the time between the planning CT scan and the treatment. CONCLUSIONS: The EPID transit dosimetry algorithm under consideration, previously described and verified in a phantom study, is feasible for use in treatment delivery verification for real patients. Two-dimensional EPID transit dosimetry can play an important role in indicating when a treatment delivery is inconsistent with the original plan.

Patterns of care for locally advanced vulvar cancer.

OBJECTIVE: Patients with locally advanced vulvar carcinoma can be treated with primary surgery or neoadjuvant chemoradiation. Neoadjuvant treatment appears to be associated with decreased morbidity and acceptable long-term outcomes. We examined the patterns of care for women with locally advanced vulvar cancer. STUDY DESIGN: Data from the Surveillance, Epidemiology, and End Results (SEER) database was used to examine women with stage III-IVA vulvar cancer treated from 1988 to 2008. Primary therapy was classified as surgery or radiation. Multivariable logistic regression models were developed to examine the use of primary radiotherapy. RESULTS: We identified a total of 2292 women including 1757 who underwent primary surgery (76.7%) and 535 treated with primary radiation (23.3%). The use of primary radiation increased with time from 18.0% in 1988 to 30.1% in 2008. In a multivariable model, older women (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.03-1.72), black women (OR, 1.59; 95% CI, 1.14-2.23), and patients with stage IVA tumors (OR, 2.23; 95% CI, 1.78-2.81) were more likely to receive primary radiation. Among women treated with primary radiotherapy, only 17.8% ultimately underwent surgical resection. CONCLUSION: The use of primary radiation for locally advanced vulvar cancer is limited but has increased over time. Multiple patient and tumor factors influence use. The majority of patients with stage III-IVA vulvar cancer treated with primary radiation therapy did not undergo surgical resection.

Uptake and outcomes of intensity-modulated radiation therapy for uterine cancer.

OBJECTIVE: While intensity-modulated radiation therapy (IMRT) allows more precise radiation planning, the technology is substantially more costly than conformal radiation and, to date, the benefits of IMRT for uterine cancer are not well defined. We examined the use of IMRT and its effect on late toxicity for uterine cancer. METHODS: Women with uterine cancer treated from 2001 to 2007 and registered in the SEER-Medicare database were examined. We investigated the extent and predictors of IMRT administration. The incidence of acute and late-radiation toxicities was compared for IMRT and conformal radiation. RESULTS: We identified a total of 3555 patients including 328 (9.2%) who received IMRT. Use of IMRT increased rapidly and reached 23.2% by 2007. In a multivariable model, residence in the western U.S. and receipt of chemotherapy were associated with receipt of IMRT. Women who received IMRT had a higher rate of bowel obstruction (rate ratio=1.41; 95% CI, 1.03-1.93), but other late gastrointestinal and genitourinary toxicities as well as hip fracture rates were similar between the cohorts. After accounting for other characteristics, the cost of IMRT was $14,706 (95% CI, $12,073 to $17,339) greater than conformal radiation. CONCLUSION: The use of IMRT for uterine cancer is increasing rapidly. IMRT was not associated with a reduction in radiation toxicity, but was more costly.

Secretory carcinoma of the breast: results from the survival, epidemiology and end results database.

BACKGROUND: Secretory carcinoma of the breast is a rare breast cancer that is associated with incidence at a young age and an indolent course. The role for breast conservation and adjuvant radiation is unknown. METHODS: The SEER database was reviewed and 83 patients were identified with secretory carcinoma of the breast between the years 1983 and 2007. Baseline characteristics were compared with χ(2) or Fisher's exact test. Overall survival (OS) and cause-specific survival (CSS) were estimated using the Kaplan-Meier method. Analyses were performed using PASW Statistics, version 18. RESULTS: Median follow-up was 70 months. Median patient age was 53 years (range 11-86 years). 29 patients (34.9%) had involved regional lymph nodes. 39 patients (47.0%) underwent lumpectomy and 44 patients (53.0%) underwent mastectomy. 35 patients (42.2%) received radiation. Patients receiving radiation were more likely to have undergone lumpectomy, and the use of radiation increased over time. 5-year OS was 87.2%; 10-year OS was 76.5%. 5-year CSS was 94.4%; 10-year CSS was 91.4%. Among the lumpectomy patients, 25 patients (64.1%) received radiation. For lumpectomy patients, those who did not receive radiation had a 5-year OS of 92.9% and 10-year OS of 72.2% while patients who did receive radiation had a 5-year OS of 95.5% and 10-year OS of 85.9%. Only 1 patient treated with lumpectomy only died of cancer (92.9% CSS) and no patients treated with lumpectomy and radiation died of cancer (100% CSS). CONCLUSIONS: Secretory carcinoma of the breast commonly occurs at a later age than previously recognized, and is associated with good long-term survival.

Endotracheal tube cuff--small important part of a big issue.

Many of the complications related to prolonged ventilation are related to inappropriate handling of endotracheal tube (ETT) cuff. This article reviews the possible complications associated with the ETT cuff, and the landmark development made in that field. The article challenges the present paradigm of cuff use and reviews the current clinical practice in that area.