Dean A. Shumway

Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States

Much of what is known about the significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is derived from single‐institution retrospective studies, post hoc analyses of tissue specimens from clinical trials, and tissue bank studies with a small sample size. The objective of this study is to investigate the impact of HPV on the frequency and clinical presentation of oropharyngeal carcinoma in a large, national sample with information from patients who underwent HPV testing.

Ageism in the Undertreatment of High-Risk Prostate Cancer: How Long Will Clinical Practice Patterns Resist the Weight of Evidence?

Age discrimination is defined as “the denial of privilege or other unfair treatment based on the age of the person who is discriminated against,” and is a topic that has been studied at length in the field of oncology. For instance, despite obtaining similar survival benefit as younger patients, elderly patients are less likely to receive either surgery or radiation therapy (RT) for oropharyngeal squamous cell carcinoma. With rectal cancer, patients older than age 65 are less likely to receive preoperative radiotherapy, which has been demonstrated to reduce local recurrence rates and is widely considered as the standard of care for intermediate and locally advanced disease. Alarmingly, age-based discrimination is especially prevalent in men with high-risk prostate cancer; some have noted that for men older than 75 years of age with high-risk prostate cancer, 67% received primary androgendeprivation therapy (ADT) or no therapy at all, and only 33% received any local therapy. With recent guidelines recommending against prostate-specific antigen screening and increased attention given to the role of active surveillance for low-risk prostate cancer, it is easy to lose sight of the fact that prostate cancer is a leading cause of cancer mortality in men, second only to lung cancer. Ultimately, the majority of men diagnosed with locally advanced or high-risk prostate cancer will succumb to their disease within 15 years with conservative treatment, regardless of their age at diagnosis. Yet numerous studies have demonstrated widespread undertreatment of high-risk prostate cancer in older men, despite the observation that older men are more likely to have high-risk disease and account for approximately half of deaths as a result of prostate cancer. Furthermore, undertreatment of high-risk prostate cancer is a growing problem, with an increasing use of primary ADT monotherapy over time. Given that an average 75-year-old man in the United States has a remaining life expectancy of 11 years, and that the 10-year cause-specific mortality from conservatively treated high-risk prostate cancer is approximately 26%, this represents a serious potential for age-dependent bias against therapy. Therefore, it is important to assess the potential benefits of both ADT and RT in the treatment of high-risk prostate cancer in elderly men. Randomized controlled trials (RCTs) performed by both the EORTC (European Organisation for Research and Treatment of Cancer) and RTOG (Radiation Therapy Oncology Group) in men who were an average of 70 years of age demonstrated that the addition of long-term ADT to RT for locally advanced prostate cancer resulted in up to a 16% absolute improvement in survival at 5 years. Initially it was unclear if the survival benefit was attributable to eradication of micrometastases with systemic therapy or to ablation of local disease that could later serve as a reservoir for metastasis. In findings from two subsequent RCTs (also in men with an average age of 70 years), adding RT to ADT demonstrated that improved local control with externalbeam RT contributed significantly to the observed survival benefits, with an absolute improvement in overall survival (OS) of 8% to 9% at 7 to 10 years. A third RCT with shorter follow-up and a smaller sample size also demonstrated improvements in clinical/biochemical progression–free survival and metastasis-free survival with the addition of RT to ADT. On the basis of these three trials, there is little question that for patients with locally advanced prostate cancer, use of ADT alone provides inadequate treatment with inferior outcomes in comparison to ADT with RT. These findings are now reflected in guidelines from the European Association of Urology, the American Urological Association, and the National Comprehensive Cancer Network, which, in essence, recommend that primary therapy with ADT alone should be considered only for patients who are not candidates for definitive therapy. How these results apply to older men who are not well represented in the prospective clinical trials is an area of critical unmet need that is in part addressed by the population-based observational study performed by Bekelman et al. Using SEER-Medicare data from patients who were treated between 1995 and 2007, the authors first restricted analysis to men similar to those enrolled onto the RCTs, focusing on men younger than 75 years of age with high-volume tumors, and their results demonstrate similar relative and absolute benefits for cause-specific and OS to those observed in the phase III trials with the addition of RT to ADT. This is an intuitive and reassuring finding: that the results observed in selected patients enrolled onto RCTs seem applicable to a similar group of men receiving care in the community. However, more importantly, the authors then extend their analysis to assess the generalizability of these findings to two groups who are not well represented in the RCTs: men with screendetected high-risk prostate cancer and elderly men older than age 75 years. Here, too, they observed substantial improvements with the addition of RT to ADT with a 50% reduction in the risk of dying as a JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 7 MARCH 1 2015

Wide Variation in the Diffusion of a New Technology: Practice-Based Trends in Intensity-Modulated Radiation Therapy (IMRT) Use in the State of Michigan, With Implications for IMRT Use Nationally

PURPOSE To characterize the adoption and variation of intensity-modulated radiation therapy (IMRT) use in the state of Michigan. METHODS As a certificate-of-need state, Michigan requires every radiation oncology facility to report the number of external-beam and IMRT treatments delivered annually. We examined the percentage of treatments delivered using IMRT across centers from 2005 to 2012. We constructed a repeated-measures longitudinal linear regression model to evaluate bivariable and multiple variable associations with IMRT use. RESULTS The median proportion of treatments delivered with IMRT rose from 16% in 2005 to 42% in 2012. All treatment centers in the state of Michigan possessed the capacity to deliver IMRT as of 2009. The fraction of treatments delivered with IMRT varied between 23% and 96% (standard deviation, 19%) in the lowest- and highest-use centers in 2012. Higher IMRT use was significantly associated with freestanding facilities and year of treatment, with a trend toward higher IMRT use in academic centers and low-volume facilities. CONCLUSION IMRT use grew significantly across the state of Michigan over time, with four-fold variability among centers, which was related to facility characteristics. These data provide no indication of an ideal or appropriate level of IMRT use. Rather, the wide variation in IMRT use among centers indicates a lack of consensus regarding the situations in which IMRT provides significant clinical benefit. This supports further research and interventions to ensure that patients receive appropriate care, regardless of where they are treated.

Treatment Experiences of Latinas After Diagnosis Of Breast Cancer

The authors examined racial/ethnic differences in patient perspectives regarding their breast cancer treatment experiences.

Surgeon Attitudes Toward the Omission of Axillary Dissection in Early Breast Cancer

Importance The American College of Surgeons Oncology Group (ACOSOG) Z0011 study demonstrated the safety of sentinel node biopsy alone in clinically node-negative women with metastases in 1 or 2 sentinel nodes treated with breast conservation. Little is known about surgeon perspectives regarding when axillary lymph node dissection (ALND) can be omitted. Objectives To determine surgeon acceptance of ACOSOG Z0011 findings, identify characteristics associated with acceptance of ACOSOG Z0011 results, and examine the association between acceptance of the Society of Surgical Oncology and American Society for Radiation Oncology negative margin of no ink on tumor and surgeon preference for ALND. Design, Setting, and Participants A survey was sent to 488 surgeons treating a population-based sample of women with early-stage breast cancer (N = 5080). The study was conducted from July 1, 2013, to August 31, 2015. Main Outcomes and Measures Surgeons were categorized as having low, intermediate, or high propensity for ALND according to the outer quartiles of ALND scale distribution. A multivariable linear regression model was used to confirm independent associations. Results Of the 488 surgeons invited to participate, 376 (77.0%) responded and 359 provided complete information regarding propensity for ALND derived from 5 clinical scenarios. Mean surgeon age was 53.7 (range, 31-80) years; 277 (73.7%) were male; 142 (37.8%) treated 20 or fewer breast cancers annually and 108 (28.7%) treated more than 50. One hundred seventy-five (49.0%) recommended ALND for 1 macrometastasis. Of low-propensity surgeons who recommended ALND, only 1 (1.1%) approved ALND for any nodal metastases compared with 69 (38.6%) and 85 (95.5%) of selective and high-propensity surgeons (P < .001), respectively. In multivariable analysis, lower ALND propensity was significantly associated with higher breast cancer volume (21-50: −0.19; 95% CI, −0.39 to 0.02; >51: −0.48; 95% CI, −0.71 to −0.24; P < .001), recommendation of a minimal margin width (1-5 mm: −0.10; 95% CI, −0.43 to 0.22; no ink on tumor: −0.53; 95% CI, −0.82 to −0.24; P < .001), participation in a multidisciplinary tumor board (1%-9%: −0.25; 95% CI, −0.55 to 0.05; >9%: −0.37; 95% CI, −0.63 to −0.11; P = .02), and Los Angeles Surveillance, Epidemiology, and End Results site (−0.18; 95% CI, −0.35 to −0.01; P = .04). Conclusions and Relevance This study shows substantial variation in surgeon acceptance of more limited surgery for breast cancer, which is associated with higher breast cancer volume and multidisciplinary interactions, suggesting the potential for overtreatment of many patients and the need for education targeting lower-volume breast surgeons.

Patient views and correlates of radiotherapy omission in a population-based sample of older women with favorable-prognosis breast cancer: Patient Views on Radiotherapy Omission

The omission of radiotherapy (RT) after lumpectomy is a reasonable option for many older women with favorable‐prognosis breast cancer. In the current study, we sought to evaluate patient perspectives regarding decision making about RT.

Development of a new photonumeric scale for acute radiation dermatitis in patients with breast cancer.

86 Background: The Common Terminology Criteria for Adverse Events (CTCAE) is frequently used to grade the severity of acute radiation dermatitis (ARD), but has not been validated despite decades of clinical use. We sought to develop a photonumeric scale to consistently describe ARD in breast cancer patients undergoing radiation (RT). METHODS Patients enrolled on a prospective study that included photographs and quantitative measurements of erythema and hyperpigmentation using colorimetry. 209 photographs from 35 patients with white skin and 369 photographs from 50 patients with skin of color were used to develop two photonumeric scales. Predominant erythema (in white skin) OR hyperpigmentation (in skin of color) were rated on a 4 point scale, with grading of desquamation on a separate 3 point scale. Four raters used both CTCAE and photonumeric scales to independently score all photographs. Intra- and inter-rater agreements were assessed using weighted kappa scores. RESULTS Using the CTCAE, 95% of photos were rated as grade 1 or 2. There was a trend toward higher grade in patients with skin of color, with grade 2 toxicity in 43% vs. 24%. Intra-rater agreement for CTCAE ratings was 65-87% (kappa 0.34-0.67), with a wide range of inter-rater agreement (56-81% agreement fraction, kappa 0.04-0.58). Using the photonumeric scale, intra-rater agreement was high for erythema/hyperpigmentation in patients with white skin (74-82%, kappa 0.49-0.70) and skin of color (69-86%, kappa 0.55-0.79), along with desquamation (78-87%, kappa 0.52-0.66). There was moderate inter-rater agreement for erythema/hyperpigmentation (51-82%, kappa 0.15-0.71) and desquamation (63-88%, kappa 0.36-0.58). Colorimetric measurements correlated strongly with photonumeric grade. CONCLUSIONS We report a new photonumeric scale for ARD in breast cancer patients with satisfactory reliability across the spectrum of skin pigmentation. Intra-physician ratings were consistent, with moderate inter-physician agreement. The CTCAE functions as a binary scale, with 95% of ARD rated as grade 1 or 2 toxicity. Future work includes correlation with patient-reported outcomes and physician ratings at the point-of-care. Funded by a Munn Idea Grant (G011480).

Provider variability in intensity modulated radiation therapy utilization among Medicare beneficiaries in the United States

BACKGROUND In this study, we sought to examine the variation in intensity modulated radiation therapy (IMRT) use among radiation oncology providers. METHODS AND MATERIALS The Medicare Physician and Other Supplier Public Use File was queried for radiation oncologists practicing during 2014. Healthcare Common Procedural Coding System code 77301 was designated as IMRT planning with metrics including number of total IMRT plans, rate of IMRT utilization, and number of IMRT plans per distinct beneficiary. RESULTS Of 2759 radiation oncologists, the median number of total IMRT plans was 26 (mean, 33.4; standard deviation, 26.2; range, 11-321) with a median IMRT utilization rate of 36% (mean, 43%; standard deviation, 25%; range, 4% to 100%) and a median number of IMRT plans per beneficiary of 1.02 (mean, 1.07; range, 1.00-3.73). On multivariable analysis, increased IMRT utilization was associated with male sex, academic practice, technical fee billing, freestanding practice, practice in a county with 21 or more radiation oncologists, and practice in the southern United States (P < .05). The top 1% of users (28 providers) billed a mean 181 IMRT plans with an IMRT utilization rate of 66% and 1.52 IMRT plans per beneficiary. Of these 28 providers, 24 had billed technical fees, 25 practiced in freestanding clinics, and 20 practiced in the South. CONCLUSIONS Technical fee billing, freestanding practice, male sex, and location in the South were associated with increased IMRT use. A small group of outliers shared several common demographic and practice-based characteristics.

Report from the SWOG Radiation Oncology Committee: Research Objectives Workshop 2017

The Radiation Therapy Committee of SWOG periodically evaluates its strategic plan in an effort to maintain a current and relevant scientific focus, and to provide a standard platform for future development of protocol concepts. Participants in the 2017 Strategic Planning Workshop included leaders in cancer basic sciences, molecular theragnostics, pharmaceutical and technology industries, clinical trial design, oncology practice, and statistical analysis. The committee discussed high-priority research areas, such as optimization of combined modality therapy, radiation oncology–specific drug design, identification of molecular profiles predictive of radiation-induced local or distant tumor responses, and methods for normal tissue-specific mitigation of radiation toxicity. The following concepts emerged as dominant questions ready for national testing: (i) what is the role of radiotherapy in the treatment of oligometastatic, oligorecurrent, and oligoprogressive disease? (ii) How can combined modality therapy be used to enhance systemic and local response? (iii) Can we validate and optimize liquid biopsy and other biomarkers (such as novel imaging) to supplement current response criteria to guide therapy and clinical trial design endpoints? (iv) How can we overcome deficiencies of randomized survival endpoint trials in an era of increasing molecular stratification factors? And (v) how can we mitigate treatment-related side effects and maximize quality of life in cancer survivors? The committee concluded that many aspects of these questions are ready for clinical evaluation and example protocol concepts are provided that could improve rates of cancer cure and quality of survival. Clin Cancer Res; 24(15); 3500–9. ©2018 AACR.

Characterizing potential bone scan overuse among men treated with radical prostatectomy

To characterise bone scan use, and potential overuse, after radical prostatectomy (RP) using data from a large, national integrated delivery system. Overuse of imaging is well documented in the setting of newly diagnosed prostate cancer, but whether overuse persists after RP remains unknown.