Andrea B. McKee

Efficacy of Oral Sildenafil in Patients With Erectile Dysfunction After Radiotherapy for Carcinoma of the Prostate

OBJECTIVES To determine the efficacy of sildenafil for patients with erectile dysfunction after radiotherapy for localized prostate cancer. METHODS Fifty patients with erectile dysfunction after radiotherapy were treated with sildenafil. Their median age was 68 years (range 54 to 78). All were treated with a three-dimensional conformal external beam radiotherapy approach, and the median dose prescribed to the planning target volume was 75.6 Gy. Patients were initially given 50 mg of sildenafil and instructed to use the medication on at least three occasions. They were then contacted to ascertain the efficacy of and tolerance to the medication. RESULTS Significant improvement in the firmness of the erection after sildenafil was reported in 37 patients (74%), 2 (4%) had partial improvement, and 11 (22%) had no response. Significant improvement in the durability of the erection was reported in 33 patients (66%), 3 (6%) had partial improvement, and 14 (28%) reported no improvement. Patients with partial or moderate erectile function before using sildenafil were more likely to benefit from the medication compared with those with absent function. Among 29 patients with erections classified as partial after radiotherapy, 26 (90%) had a significant response to the medication. In contrast, only 11 (52%) of 21 with erections classified as flaccid after radiotherapy had a significant response to the medication (P = 0.007). CONCLUSIONS Sildenafil improved erectile function in greater than two thirds of patients with postradiotherapy impotence. Patients with less severe dysfunction are most likely to benefit from this intervention.

IS THERE A DIFFERENCE IN OUTCOME BETWEEN STAGE I-II ENDOMETRIAL CANCER OF PAPILLARY SEROUS/CLEAR CELL AND ENDOMETRIOID FIGO GRADE 3 CANCER?

PURPOSE Several reports in the literature have shown that, compared with endometrioid adenocarcinoma, patients with papillary serous (PS) and clear cell (CC) histologic features do worse. However, it is unclear whether the outcome of PS/CC cancer is different from that of poorly differentiated endometrioid cancer. The purpose of this study was to compare the outcome between PS/CC and endometrioid International Federation of Gynecology and Obstetrics (FIGO) Grade 3 cancer and was limited to patients with Stage I-II uterine carcinoma. METHODS AND MATERIALS Between November 1987 and September 1999, 83 patients with Stage I endometrial cancer and Stage II occult endometrial cancer were treated with simple hysterectomy and high-dose-rate intravaginal brachytherapy. Forty-one patients (49%) had FIGO Grade 3 endometrioid tumors (Group 1) and 42 (51%) had PS/CC histologic features (Group 2). The mean age was 63 years (range 30-89). Comprehensive surgical staging was done in 23 (28%) of 83 patients. Capillary space-like invasion (CSLI) was seen in 24 (29%) of 83 patients. The median dose of intravaginal brachytherapy when used alone was 21 Gy in 3 fractions. Additional external beam radiotherapy was given to 42 (51%) of 83 patients to 45 Gy. The two groups were balanced with regard to age, race, comprehensive surgical staging, amount of myometrial involvement, CSLI, lower uterine segment involvement, cervical involvement, and use of external beam radiotherapy. The median follow-up was 46 months (range 4-147). RESULTS The pattern of relapse was as follows: vagina/pelvis in 5 of 14 patients, lungs in 8 of 15, intra-abdominal in 4 of 12, and supraclavicular lymph nodes in 1 of 14. One of the four intra-abdominal disseminations was in Group 1 and the other three in Group 2 (p = 0.6). The 5-year vaginal/pelvic control, disease-free survival (DFS), and overall survival (OS) rate was 93% (95% confidence interval [CI] 87-99%), 79% (95% CI 69-89%), and 74% (95% CI 64-85%), respectively. No significant difference in outcome was found between Groups 1 and 2. The 5-year vaginal/pelvic control rate was 97% (95% CI 91-100%) in Group 1 compared with 90% (95% CI 81-99%) in Group 2 (p = 0.2). The 5-year DFS rate was 79% (95% CI 64-95%) in Group 1 vs. 78% (95% CI 65-92%) in Group 2 (p = 0.6), and the 5-year OS rate was 71% (95% CI 55-87%) in Group 1 vs. 79% (95% CI 66-92%) in Group 2 (p = 0.3). The influence on outcome of age, race, comprehensive surgical staging, CSLI, amount of myometrial invasion, cervical involvement, lower uterine segment involvement, and presence of pure PS or CC histologic features was evaluated. On multivariate analysis, only CSLI correlated with poor DFS (p = 0.04; relative risk 3, 95% CI 1-9) and OS (p = 0.02; relative risk 3, 95% CI 1-6). CONCLUSION On the basis of the results of this study, no significant difference in outcome exists between patients with Stage I-II endometrial cancer with PS/CC histologic features and those with similar stage disease, but with FIGO Grade 3 endometrioid histologic features. CSLI was the only independent predictor of poor DFS and OS.

Performance of ACR Lung-RADS in a Clinical CT Lung Screening Program

PURPOSE The aim of this study was to assess the effect of applying ACR Lung-RADS in a clinical CT lung screening program on the frequency of positive and false-negative findings. METHODS Consecutive, clinical CT lung screening examinations performed from January 2012 through May 2014 were retroactively reclassified using the new ACR Lung-RADS structured reporting system. All examinations had initially been interpreted by radiologists credentialed in structured CT lung screening reporting following the National Comprehensive Cancer Networks Clinical Practice Guidelines in Oncology: Lung Cancer Screening (version 1.2012), which incorporated positive thresholds modeled after those in the National Lung Screening Trial. The positive rate, number of false-negative findings, and positive predictive value were recalculated using the ACR Lung-RADS-specific positive solid/part-solid nodule diameter threshold of 6 mm and nonsolid (ground-glass) threshold of 2 cm. False negatives were defined as cases reclassified as benign under ACR Lung-RADS that were diagnosed with malignancies within 12 months of the baseline examination. RESULTS A total of 2,180 high-risk patients underwent baseline CT lung screening during the study interval; no clinical follow-up was available in 577 patients (26%). ACR Lung-RADS reduced the overall positive rate from 27.6% to 10.6%. No false negatives were present in the 152 patients with >12-month follow-up reclassified as benign. Applying ACR Lung-RADS increased the positive predictive value for diagnosed malignancy in 1,603 patients with follow-up from 6.9% to 17.3%. CONCLUSIONS The application of ACR Lung-RADS increased the positive predictive value in our CT lung screening cohort by a factor of 2.5, to 17.3%, without increasing the number of examinations with false-negative results.

Intravaginal high-dose-rate brachytherapy for Stage IB (FIGO Grade 1, 2) endometrial cancer.

PURPOSE To evaluate the outcome of patients with Stage IB Grades 1 and 2 endometrial cancer treated with adjuvant high-dose-rate intravaginal brachytherapy. METHODS AND MATERIALS Between November 1987 and October 1999, 233 patients with Stage IB FIGO Grades 1 and 2 were treated with postoperative adjuvant high-dose-rate intravaginal brachytherapy. The median dose was 21 Gy in 7 Gy/fraction given at 2-week intervals. The mean age was 60 years. All patients underwent simple hysterectomy. Comprehensive surgical staging, defined as pelvic washing and pelvic and paraaortic lymph nodes sampling, was done in 9% of patients. Patients with FIGO Grade 3, papillary serous cancer, or clear-cell cancer were excluded from this analysis. Complications were assessed in terms of late Radiation Therapy Oncology Group toxicity (Grade > or =3) of the gastrointestinal tract, genitourinary tract, and vagina. RESULTS With a median follow-up of 57 months, the 5-year vaginal/pelvic control, disease-free survival, and overall survival rate was 96% (95% confidence interval [CI] 94-99%), 94% (95% CI 91-98%), and 94% (95% CI 91-98%), respectively. The influence on outcome of age, grade (1 vs. 2), depth of invasion (one-third or less or greater than one-third), capillary space-like invasion, lower uterine segment involvement, and comprehensive surgical staging was evaluated. None of these factors significantly affected the rate of vaginal/pelvic control. Only age > or =60 years influenced the outcome for disease-free and overall survival. The 5-year rate for both disease-free and overall survival was 90% (95% CI 84-97%) for patients > or =60 years old compared with 99% (95% CI 96-100%) for those <60 years (p = 0.03 and 0.005, respectively). Of 233 patients, 3 (1%) developed Grade 3 or greater complications, with a 5-year actuarial rate of 2% (95% CI 0-5%). Two patients developed Grade 3 genitourinary toxicity, and 1 Grade 4 vaginal toxicity. CONCLUSION On the basis of this retrospective study, adjuvant postoperative high-dose-rate intravaginal brachytherapy provides excellent outcomes and acceptable morbidity. These results compare very favorably with those reported in the literature using surgery alone or with pelvic radiation.

Initial experience with a free, high-volume, low-dose CT lung cancer screening program.

The National Lung Screening Trial demonstrated a significant mortality benefit for patients at high risk for lung cancer undergoing serial low-dose CT. Currently, the National Comprehensive Cancer Network and several United States-based professional associations recommend CT Lung screening for high-risk patients. In the absence of established reimbursement, the authors modeled and implemented a free low-dose CT lung cancer screening program to provide equitable access to all eligible patients. Elements of the program reported in this article include a decentralized referral network, centralized program coordination, structured reporting, and a patient data management system. The experience and initial results observed in this clinical setting closely match the performance metrics of the National Lung Screening Trial with regard to cancer detection and incidental findings rates. To eliminate health care disparities a vigorous lobbying effort will be needed to expedite reimbursement and make CT lung screening equally available to all patients at high-risk.

Surgical Prehabilitation in Patients with Cancer: State-of-the-Science and Recommendations for Future Research from a Panel of Subject Matter Experts

This review by a 10-member panel of experts in surgical prehabilitation addresses processes that may improve oncologic care. Surgical prehabilitation is the process on the continuum of care that occurs between the time of cancer diagnosis and the beginning of surgical treatment. The panel focused on the current state-of-the-science and recommended future research that would help to identify the elements that enhance preoperative physical, nutritional, and psychological health in anticipation of surgery, mitigate the burden of disease, facilitate the return of patient health status to baseline values, decrease postoperative morbidity, and reduce health care costs.

Lung Cancer Screening

Lung cancer is the leading cause of cancer-related death among men and women in the U.S. and worldwide. For many decades, lung cancer was the sole cancer among the deadly four without an evidence-based screening method for decreasing mortality. This changed in November 2011, when findings from the National Lung Cancer Screening Trial showed low-dose lung CT screening was more efficacious in reducing deaths in high-risk individuals than conventional radiography. As such, an ever-increasing number of health organizations now recommend this screening protocol.Lung Cancer Screening by Mark Parker and esteemed VCU Health colleagues, fulfills the dire need for a comprehensive guide explaining the crucial aspects of lung cancer screenings. The first two chapters lay a foundation with discussion of lung cancer epidemiology and risk factors beyond cigarette smoking. Subsequent chapters cover the fundamentals, with clinical pearls on setting up a successful lung cancer screening program, patient eligibility criteria, imaging variances of tumors in the lungs, screening pros and cons, and interpreting/reporting screening results.The evolution and future of lung cancer screeningsDetection and management of unexpected incidental pulmonary and non-pulmonary findingsDiscussion of test cases utilizing the Lung-RADSTM risk-stratifying system for low-dose chest CT screeningsBenefits and potential harms associated with mass lung cancer screening programs including false positive, false negative, and over-diagnosis rates

Preliminary evaluation of a telephone-based smoking cessation intervention in the lung cancer screening setting: A randomized clinical trial

Incorporating effective smoking cessation interventions into lung cancer screening (LCS) programs will be essential to realizing the full benefit of screening. We conducted a pilot randomized trial to determine the feasibility and efficacy of a telephone-counseling (TC) smoking cessation intervention vs. usual care (UC) in the LCS setting. In collaboration with 3 geographically diverse LCS programs, we enrolled current smokers (61.5% participation rate) who were: registered to undergo LCS, 50-77 years old, and had a 20+ pack-year smoking history. Eligibility was not based on readiness to quit. Participants completed pre-LCS (T0) and post-LCS (T1) telephone assessments, were randomized to TC (N=46) vs. UC (N=46), and completed a final 3-month telephone assessment (T2). Both study arms received a list of evidence-based cessation resources. TC participants also received up to 6 brief counseling calls with a trained cessation counselor. Counseling calls incorporated motivational interviewing and utilized the screening result as a motivator for quitting. The outcome was biochemically verified 7-day point prevalence cessation at 3-months post-randomization. Participants (56.5% female) were 60.2 (SD=5.4) years old and reported 47.1 (SD=22.2) pack years; 30% were ready to stop smoking in the next 30 days. TC participants completed an average of 4.4 (SD=2.3) sessions. Using intent-to-treat analyses, biochemically verified quit rates were 17.4% (TC) vs. 4.3% (UC), p<.05. This study provides preliminary evidence that telephone-based cessation counseling is feasible and efficacious in the LCS setting. As millions of current smokers are now eligible for lung cancer screening, this setting represents an important opportunity to exert a large public health impact on cessation among smokers who are at very high risk for multiple tobacco-related diseases. If this evidence-based, brief, and scalable intervention is replicated, TC could help to improve the overall cost-effectiveness of LCS. TRIAL REGISTRATION NCT02267096, https://clinicaltrials.gov.

Outcome of primary soft tissue sarcoma of the knee and elbow

PURPOSE Concern is frequently raised regarding the tolerance of irradiation over a joint space. The purpose of this study was to determine the outcome in terms of relapse and potential complications in patients with knee and elbow soft tissue sarcoma treated with limb-sparing surgery with or without adjuvant radiotherapy (RT). METHODS AND MATERIALS A review of our prospective database between June 1982 and December 1999 identified 86 adult patients with primary soft tissue sarcoma arising from the knee (n = 65; 76%) or elbow (n = 21; 24%) treated with limb-sparing surgery. Tumors had high-grade histologic features in 72% and were >5 cm in 48% of patients. Adjuvant RT was given to 46 (54%) of 86 patients. The type of RT was postoperative external beam RT in 63% and brachytherapy in 37%. Of the 46 patients who received RT, 85% (n = 39) had deep, 78% (n = 36) high-grade, and 54% (n = 25) >5-cm tumors. Complications were assessed in terms of wound complications requiring repeated surgery, bone fracture, nerve damage, and joint stiffness. RESULTS With a median follow-up of 48 months (range 4-175), the 5-year actuarial rate of local control, distant control, and overall survival was 75% (95% confidence interval [CI] 64-85%), 82% (95% CI 73-91%), and 81% (95% CI 71-91%), respectively. The 5-year local control rate for patients who received RT was 80% vs. 71% for those who did not (p = 0.3). The type of RT did not significantly influence the local control rate. Patients treated with external beam RT had a 5-year local control rate of 84% compared with 73% for those treated with brachytherapy (p = 0.4). On multivariate analysis, tumor size >5 cm retained its significance as an independent predictor of poor local control (p = 0.04; relative risk 3; 95% CI 1-6). In addition, high-grade histologic features emerged as an independent predictor of local recurrence (p = 0.02; relative risk 4; 95% CI 1-20). No statistically significant difference was found between the RT and no-RT group in terms of the 5-year actuarial rate of wound reoperation (10% vs. 3%, p = 0.1), bone fracture (3% vs. 5%, p = 0.5), or nerve damage (6% vs. 3%, p = 0.5). Joint stiffness was significantly higher in the RT group (24% vs. 0%, p = 0.001), but this stiffness was severe to moderate in only 2 patients. CONCLUSION On the basis of the findings of this retrospective review, adjuvant RT seems to be relatively well tolerated despite the inclusion of part of the joint space in the irradiation portal. Joint stiffness was seen more frequently with adjuvant RT, but it was moderate to severe in only a small number of patients.

Low-dose computed tomography screening for lung cancer in a clinical setting: essential elements of a screening program.

The purpose of this article is to review clinical computed tomography (CT) lung screening program elements essential to safely and effectively manage the millions of Americans at high risk for lung cancer expected to enroll in lung cancer screening programs over the next 3 to 5 years. To optimize the potential net benefit of CT lung screening and facilitate medical audits benchmarked to national quality standards, radiologists should interpret these examinations using a validated structured reporting system such as Lung-RADS. Patient and physician educational outreach should be enacted to support an informed and shared decision-making process without creating barriers to screening access. Programs must integrate smoking cessation interventions to maximize the clinical efficacy and cost-effectiveness of screening. At an institutional level, budgets should account for the necessary expense of hiring and/or training qualified support staff and equipping them with information technology resources adequate to enroll and track patients accurately over decades of future screening evaluation. At a national level, planning should begin on ways to accommodate the upcoming increased demand for physician services in fields critical to the success of CT lung screening such as diagnostic radiology and thoracic surgery. Institutions with programs that follow these specifications will be well equipped to meet the significant oncoming demand for CT lung screening services and bestow clinical benefits on their patients equal to or beyond what was observed in the National Lung Screening Trial.