W. Warren Suh

Recommendations on the Use of 18F-FDG PET in Oncology

The rationale was to develop recommendations on the use of 18F-FDG PET in breast, colorectal, esophageal, head and neck, lung, pancreatic, and thyroid cancer; lymphoma, melanoma, and sarcoma; and unknown primary tumor. Outcomes of interest included the use of 18F-FDG PET for diagnosing, staging, and detecting the recurrence or progression of cancer. Methods: A search was performed to identify all published randomized controlled trials and systematic reviews in the literature. An additional search was performed to identify relevant unpublished systematic reviews. These publications comprised both retrospective and prospective studies of varied methodologic quality. The anticipated consequences of false-positive and false-negative tests when evaluating clinical usefulness, and the impact of 18F-FDG PET on the management of cancer patients, were also reviewed. Results and Conclusion: 18F-FDG PET should be used as an imaging tool additional to conventional radiologic methods such as CT or MRI; any positive finding that could lead to a clinically significant change in patient management should be confirmed by subsequent histopathologic examination because of the risk of false-positive results. 18F-FDG PET should be used in the appropriate clinical setting for the diagnosis of head and neck, lung, or pancreatic cancer and for unknown primary tumor. PET is also indicated for staging of breast, colon, esophageal, head and neck, and lung cancer and of lymphoma and melanoma. In addition, 18F-FDG PET should be used to detect recurrence of breast, colorectal, head and neck, or thyroid cancer and of lymphoma.

Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature.

Among men who experience prostate‐specific antigen (PSA) failure after external beam radiation or brachytherapy (RT), many will harbor occult micrometastases; however, a significant minority will have a true local‐only failure and, thus, potentially may benefit from a salvage local therapy. Those most likely to have a local‐only failure initially have low‐risk disease (PSA < 10 ng/mL, Gleason score ≤6, clinical T1c or T2a tumor status), pretreatment PSA velocity < 2.0 ng/mL per year at the time of initial presentation, interval to PSA failure > 3 years, PSA doubling time > 12 months, negative bone scan and pelvic imaging, and positive rebiopsy. In addition, men with presalvage PSA levels > 10 ng/mL, presalvage T3/T4 disease, or presalvage Gleason scores ≥7 on a rebiopsy sample without significant RT effects are unlikely to be cured by salvage local therapy. Based on a review of all series of post‐RT salvage prostatectomy, cryosurgery, and brachytherapy published in English since 1990, morbidity can be substantial. Although urinary incontinence appeared to be greater after salvage prostatectomy (41%) or cryosurgery (36%) than after brachytherapy (6%), patients who received salvage brachytherapy faced a 17% risk of grade 3 or 4 genitourinary complications and a fistula risk that averaged 3.4% across all series. From this review, the authors concluded that prospective randomized studies are needed to determine the relative efficacy of the 3 major local salvage modalities and that additional research is needed to identify factors associated with an increased risk of significant complications to improve patient selection and to augment the benefit/risk ratio associated with attempts to cure local‐only recurrences after radiation therapy. Cancer 2007.

Magnetic Resonance Image-guided Salvage Brachytherapy After Radiation in Select Men Who Initially Presented With Favorable-risk Prostate Cancer A Prospective Phase 2 Study

The authors prospectively evaluated the late gastrointestinal (GI) and genitourinary (GU) toxicity and prostate‐specific antigen (PSA) control of magnetic resonance imaging (MRI)‐guided brachytherapy used as salvage for radiation therapy (RT) failure.

Updated Results of Magnetic Resonance Imaging Guided Partial Prostate Brachytherapy for Favorable Risk Prostate Cancer: Implications for Focal Therapy

PURPOSE We report updated results of magnetic resonance imaging guided partial prostate brachytherapy and propose a definition of biochemical failure following focal therapy. MATERIALS AND METHODS From 1997 to 2007, 318 men with cT1c, prostate specific antigen less than 15 ng/ml, Gleason 3 + 4 or less prostate cancer received magnetic resonance imaging guided brachytherapy in which only the peripheral zone was targeted. To exclude benign prostate specific antigen increases due to prostatic hyperplasia, we investigated the usefulness of defining prostate specific antigen failure as nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year. Cox regression was used to determine the factors associated with prostate specific antigen failure. RESULTS Median followup was 5.1 years (maximum 12.1). While 36 patients met the nadir +2 criteria, 16 of 17 biopsy proven local recurrences were among the 26 men who also had a prostate specific antigen velocity greater than 0.75 ng/ml per year (16 of 26 vs 1 of 10, p = 0.008). Using the nadir +2 definition, prostate specific antigen failure-free survival for low risk cases at 5 and 8 years was 95.1% (91.0-97.3) and 80.4% (70.7-87.1), respectively. This rate improved to 95.6% (91.6-97.7) and 90.0% (82.6-94.3) using nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year. For intermediate risk cases survival was 73.0% (55.0-84.8) at 5 years and 66.4% (44.8-81.1) at 8 years (the same values as using nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year). CONCLUSIONS Requiring a prostate specific antigen velocity greater than 0.75 ng/ml per year in addition to nadir +2 appears to better predict clinical failure after therapies that target less than the whole gland. Further followup will determine whether magnetic resonance imaging guided brachytherapy targeting the peripheral zone produces comparable cancer control to whole gland treatment in men with low risk disease. However, at this time it does not appear adequate for men with even favorable intermediate risk disease.

American Society for Radiation Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the transperineal permanent brachytherapy of prostate cancer.

Transperineal permanent prostate brachytherapy is a safe and efficacious treatment option for patients with organ-confined prostate cancer. Careful adherence to established brachytherapy standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and American Society for Therapeutic Radiation Oncology (ASTRO) has produced a practice guideline for permanent prostate brachytherapy. The guideline defines the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist and dosimetrist. Factors with respect to patient selection and appropriate use of supplemental treatment modalities such as external beam radiation and androgen suppression therapy are discussed. Logistics with respect to the brachytherapy implant procedure, the importance of dosimetric parameters, and attention to radiation safety procedures and documentation are presented. Adherence to these practice guidelines can be part of ensuring quality and safety in a successful prostate brachytherapy program.

PARTIAL-BREAST IRRADIATION VERSUS WHOLE-BREAST IRRADIATION FOR EARLY-STAGE BREAST CANCER: A COST-EFFECTIVENESS ANALYSIS

PURPOSE Accelerated partial-breast irradiation (PBI) is a new treatment paradigm for patients with early-stage breast cancer. Although PBI may lead to greater local recurrence rates, it may be cost-effective because of better tolerability and lower cost. We aim to determine the incremental cost-effectiveness of PBI compared with whole-breast radiation therapy (WBRT) for estrogen receptor-positive postmenopausal women treated for early-stage breast cancer. METHODS AND MATERIALS We developed a Markov model to describe health states in the 15 years after radiotherapy for early-stage breast cancer. External beam (EB) and MammoSite (MS) PBI were considered and assumed to be equally effective, but carried different costs. Patients received tamoxifen, but not chemotherapy. Utilities, recurrence risks, and costs were adapted from the literature; the baseline utility for no disease after radiotherapy was set at 0.92. Probabilistic sensitivity analyses were performed to model uncertainty in the PBI hazard ratio, recurrence pattern, and patient utilities. Costs (in 2004 US dollars) and quality-adjusted life-years were discounted at 3%/y. RESULTS The incremental cost-effectiveness ratio for WBRT compared with EB-PBI was

Radiation With or Without 6 Months of Androgen Suppression Therapy in Intermediate- and High-Risk Clinically Localized Prostate Cancer: A Postrandomization Analysis by Risk Group

630,000/quality-adjusted life-year; WBRT strongly dominated MS-PBI. One-way sensitivity analysis found that results were sensitive to PBI hazard ratio, recurrence pattern, baseline recurrence risk, and no evidence of disease PBI utility values. Probabilistic sensitivity showed that EB-PBI was the most cost-effective technique over a wide range of assumptions and societal willingness-to-pay values. CONCLUSIONS EB-PBI was the most cost-effective strategy for postmenopausal women with early-stage breast cancer. Unless the quality of life after MS-PBI proves to be superior, it is unlikely to be cost-effective.

Patient-reported acute gastrointestinal symptoms during concurrent chemoradiation treatment for rectal cancer†

PURPOSE Six months of androgen suppression therapy (AST) plus radiation (RT) prolongs survival vs. RT alone in men with unfavorable risk localized prostate cancer (PCa), but it is unknown if this benefit applies to all risk subgroups and, in particular, the intermediate-risk group. METHODS AND MATERIALS Among 206 men with stages T1b to T2b PCa and either a prostate-specific antigen level of >10 or a Gleason score of > or =7 or MRI evidence of T3 disease randomized to receive 70 Gy of RT with or without 6 months of AST, Cox multivariable analysis was used to assess the impact of AST on overall survival in intermediate- and high-risk localized PCa, adjusting for age, Adult Comorbidity Evaluation 27 comorbidity score, interaction between comorbidity and treatment, and known prognostic factors. Survival estimates were compared using a two-sided log-rank test. RESULTS After an 8.2-year median follow-up, 74 men died. Compared to treatment with AST plus RT, treatment with RT alone was associated with an increased risk of death in intermediate-risk (adjusted hazard ratio, 3.0 [95% confidence interval, 1.3-7.2]; p = 0.01) and high-risk PCa (adjusted hazard ratio, 3.3 [95% confidence interval, 0.94-11.3]; p = 0.06). The survival benefit of adding AST was restricted to men with no or mild comorbidity in both the intermediate-risk (90.9% vs. 85.8% survival, respectively, at 7 years for AST plus RT vs. RT alone; p = 0.009) and high-risk (88.9% vs. 51.2% survival, respectively, at 7 years for AST plus RT vs. RT alone; p = 0.007) subgroups. CONCLUSIONS In men with localized PCa who have no or mild comorbidity, adding 6 months of AST to RT was associated with improved survival for those with both intermediate-risk and high-risk disease, but in men with moderate to severe comorbidity, no benefit was observed in either risk group.

ACR Appropriateness Criteria® Resectable Rectal Cancer

Although it is known that standard 5‐fluorouracil–based chemoradiation therapy for rectal cancer causes significant acute gastrointestinal (GI) toxicity, research on patient‐reported outcomes (PROs) is limited. The authors undertook the current study to assess the feasibility of incorporating PRO measurement into routine clinical practice and to describe the trajectory of symptom development during treatment.

ACR Appropriateness Criteria®: Local Excision in Early-Stage Rectal Cancer

The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The use of IMRT requires knowledge of the patterns of spreads and anatomy. Clinical trials demonstrate high variability in target delineation without specific guidance demonstrating the need for peer review and the use of a consensus atlas. Concomitant with radiation, fluorouracil based chemotherapy remains the standard, and although toxicity is decreased with continuous infusion fluorouracil, oral capecitabine is non-inferior to the continuous infusion regimen. Additional chemotherapeutic agents, including oxaliplatin, continue to be investigated, however currently should only be utilized on clinical trials as increased toxicity and no definitive benefit has been demonstrated in clinical trials.The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.