From planned neck dissection to PET response to circulating tumour DNA: changes in post-treatment assessment of HPV-driven oropharyngeal cancer†.

INTRODUCTION: Circulating tumour human papillomavirus DNA (ctHPVDNA) is an emerging tool to assess post-treatment response in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Its use is not a standard practice, however, with interval F-18 FDG PET/CT and fiberoptic examination preferred. Post-treatment PET/CT at 3 months has a low positive predictive value (PPV), especially in patients with HPV+ OPSCC treated with (chemo)radiation therapy (CRT). We aimed to compare 3-6 month post-treatment PET/CT and ctHPVDNA test results to determine the most effective option for post-treatment response assessment. METHODS: Patients with HPV+ OPSCC that underwent commercially available ctHPVDNA blood testing after curative intent treatment were identified. Demographic, clinical, treatment, surveillance and oncologic outcome information were collected for each patient. Specificity and false positive rate were calculated for post-treatment PET/CT and ctHPVDNA. RESULTS: 80% of patients had Stage I disease. 52% of the population was treated with definitive chemoradiation (43%) or accelerated radiation (9%), with the remaining patients treated with transoral robotic surgery (TORS) +/- risk-adapted adjuvant therapy. In total, 25 patients underwent ctHPVDNA testing and PET/CT at 3-6 months after finishing treatment. At 3-6 months post-treatment, specificity of ctHPVDNA and PET/CT was 96% and 56%, correlating to false positive rates of 4% and 44%, respectively. CONCLUSIONS: ctHPVDNA is more reliable than PET/CT following treatment in patients with HPV+ OPSCC, and its incorporation in post-treatment response assessment will decrease the rate of anxiety over persistent disease and lead to a decrease in unnecessary medical procedures, including completion of neck dissection.

Multicancer Early Detection Tests: An Overview of Early Results From Prospective Clinical Studies and Opportunities for Oncologists.

A multitude of blood-based multicancer early detection (MCED) tests assessing cancer-related alterations in circulating genomic analytes and other associated signatures are currently being developed with the potential to disrupt current single-organ screening paradigms. Pathways for clinical implementation of these novel MCED tests have not been delineated, particularly for the patients with signal positive results requiring additional confirmatory testing. In this overview, we highlight early results from prospective clinical studies testing the efficacy of genomic MCED tests in cohorts of patients without known cancer diagnoses. Additionally, we discuss a proposed professional expansion of the oncology practice relating to the diagnostic workup of individuals found to have an MCED signal positive for cancer. As MCED blood tests have the potential to dramatically upend current cancer screening paradigms and downstream cancer therapy, it is imperative for oncologists to be aware of important clinical studies and the multitude of unanswered questions. The current gaps in the clinical implication of these tests may serve as a meaningful and rewarding expansion of oncology practice.

Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer: Benefit or Caution?

OBJECTIVES: In the era of dose-escalated prostate radiation therapy (RT), the use of androgen deprivation therapy (ADT) is undefined for intermediate-risk (IR) prostate cancer. There is growing concern of the risk of ADT to be detrimental to quality of life. This single-institution retrospective analysis aimed to evaluate outcomes of IR patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with or without concurrent/adjuvant short-term ADT. MATERIALS AND METHODS: Data was collected from 260 consecutive patients treated with dose-escalated IMRT with daily image-guided RT for newly diagnosed IR prostate cancer. Biochemical recurrence-free survival (BCRFS), distant metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were calculated using Kaplan-Meier methodology. RESULTS: Median follow-up was 93 months. A total of 181 patients had unfavorable IR disease, and 36.2% (N=94) received ADT, with median ADT duration of 6 months. Seven-year BCRFS was 94.1% vs. 86.2% (P=0.067), for ADT and no ADT, respectively, and no difference in distant metastasis-free survival or prostate cancer-specific survival was observed. ADT was associated with significantly worse 7-year OS (80.0% vs. 91.3%, P=0.010). Analysis of the unfavorable IR cohort alone, showed similar results; 7-year BCRFS and 7-year OS in patients who received ADT versus no ADT were 93.7% vs. 85.9% (P=0.093), and 79.0% vs. 90.6% (P=0.019), respectively. CONCLUSIONS: In our 15-year experience treating IR prostate cancer with dose-escalated IMRT with daily image-guided RT, short-term concurrent ADT was associated with a statistically significant worse OS. Additional studies are needed to determine if ADT is beneficial or detrimental for patients with IR prostate cancer treated with dose-escalated radiation.

Impact of Enlarged Nonhypermetabolic Lymph Nodes on Outcomes After Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer.

BACKGROUND: Up to 15% of patients undergoing positron emission tomography (PET)/computed tomography (CT) before stereotactic body radiotherapy (SBRT) harbor occult nodal disease. In the absence of invasive mediastinal staging, the clinical significance of enlarged nonhypermetabolic lymph nodes (LNs) remains unclear. We performed what is to our knowledge the first study to address whether enlarged nonhypermetabolic LNs were associated with higher post-SBRT failure rates. PATIENTS AND METHODS: Two academic centers assessed 157 consecutive patients treated with SBRT for cT1-2aN0M0 non-small-cell lung cancer who underwent PET/CT without pathologic nodal staging. The cutoff of an enlarged node was ≥ 1.0 cm, although a 7 mm threshold was also evaluated. Local recurrence-free survival (RFS), regional RFS, distant metastasis-free survival, RFS, and overall survival (OS) were calculated by Kaplan-Meier methodology. Multivariate Cox modeling addressed factors associated with RFS and OS. RESULTS: There were 120 patients (76%) with LNs < 1 cm and 37 (24%) with nodes ≥ 1 cm. Most patients had peripheral and/or T1 tumors. Median follow-up was 25.5 months. There were no differences between cohorts in actuarial local RFS, regional RFS, distant metastasis-free survival, RFS, or OS (P > .05 for all). Thirteen percent of patients experienced any nodal relapse, 15% of which occurred in the same station as that of the largest pre-SBRT LN. Stratification by largest LN location in an N1 versus N2 station showed no differences in RFS or OS (P > .05 for both). A 7 mm cutoff also showed no differences in outcomes (P > .05 for all). LN size was not correlated with RFS/OS on multivariable analysis (P > .05 for both). CONCLUSION: The presence of enlarged nonhypermetabolic LNs on PET/CT is not associated with increased post-SBRT failure rates.

National Practice Patterns for Clinical T1N0 Nasopharyngeal Cancer in the Elderly: A National Cancer Data Base Analysis.

BACKGROUND: The standard of care for T1N0 nasopharyngeal cancer (NPC) is definitive radiation therapy (RT). However, practice patterns in the elderly may not necessarily follow national guidelines. Herein, we investigated national practice patterns for T1N0 NPC. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) in patients ≥70 years old. Patient, tumor, and treatment parameters were extracted. Kaplan-Meier analysis was used to compare overall survival (OS) between patients receiving RT versus those under observation. Logistic regression was used to examine variables associated with receipt of RT. Cox proportional hazards modeling determined variables associated with OS. Landmark analysis of patients surviving 1 year or more was performed to assess survival differences between groups. RESULTS: In total, data of 147 patients were analyzed. RT was delivered to 89 patients (61%), whereas 58 (39%) patients underwent observation. On multivariable analysis, older patients were less likely to receive RT (p=0.003), but there were no differences between groups in terms of Charlson-Deyo comorbidity index. Median and 5-year OS in patients receiving RT versus those under observation were 71 and 33 months, and 59% and 48% (p=0.011), respectively. For patients surviving 1 year or more (n=96), there was a strong trend showing that receipt of RT was associated with better median and 5-year OS. CONCLUSION: This National Data Base analysis shows that observation is relatively common for T1N0 NPC in the elderly, but is associated with poorer survival.

Current Practice Patterns Surrounding Fertility Concerns in Stage I Seminoma Patients: Survey of United States Radiation Oncologists.

PURPOSE: Patients with testicular seminoma may face fertility issues because of their underlying disease as well as treatments they undergo. The current patterns of practice among U.S. radiation oncologists aimed at assessing and preserving fertility in patients with Stage I seminoma are unknown. METHODS: We surveyed practicing U.S. radiation oncologists via an Institutional Review Board-approved online questionnaire. Respondents' characteristics and perceived patient infertility rates were analyzed for association with treatment recommendations. RESULTS: We received 353 responses, of whom one quarter (23%) consider themselves experts. A vast majority (84%) recommend observation as a default strategy. Fifty-two percent routinely advise fertility assessment for patients before observation or chemotherapy, and 74% routinely do so before adjuvant radiation therapy (RT). Forty-one percent and 43% believe that 10% and 30% of patients are infertile following orchiectomy, respectively. Thirty-seven percent and 22% believe infertility rates following para-aortic RT to be 30% and 50%, respectively. Eighty percent routinely use clamshell scrotal shielding. Responders with higher perceived infertility rates are more likely to recommend fertility assessment/sperm banking (Fisher's exact p < 0.0001). Responders who routinely advised fertility assessment were more likely to use clamshell shielding (Cochran-Armitage trend test p = 0.0007). Clamshell use was positively correlated with higher perceived infertility rates following para-aortic RT (Spearman's correlation coefficient = 0.006). CONCLUSIONS: Despite a clear knowledge of fertility issues in men diagnosed with seminoma, there is no universal adoption of fertility assessment among U.S. radiation oncologists.

Outcomes of invasive mediastinal nodal staging versus positron emission tomography staging alone for early-stage non-small cell lung cancer treated with stereotactic body radiation therapy.

BACKGROUND: The benefit of invasive mediastinal nodal staging (IMNS) in addition to positron emission tomography-computed tomography (PET/CT) is undefined for early stage non-small cell lung cancer (NSCLC). This multi-institutional investigation aimed to evaluate outcomes and patterns of failure in patients staged with PET/CT with or without additional IMNS. METHODS: Two academic centers assessed all consecutive patients staged with PET/CT for early-stage, primary lung NSCLC (cT1-2aN0M0) treated with SBRT. Local recurrence-free survival (LRFS), nodal recurrence-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using Kaplan-Meier methodology. Univariate and multivariate Cox proportional hazards modeling addressed factors associated with outcomes. RESULTS: Overall, 180 patients (199 lesions) were staged with PET/CT alone and 56 patients (58 lesions) underwent additional IMNS. Among patients receiving IMNS, 52 (93%) underwent EBUS and 4 (7%) underwent mediastinoscopy. At a median follow-up of 33.5 months (range, 1.9-80.9 months), there was no significant difference in LRFS (37 vs. 47 months, p=0.309), NRFS (34 vs. 42 months p=0.370), DMFS (36 vs. 47 months, p=0.234) or OS (37 vs. 47 months, p=0.236) between patients undergoing PET/CT-only versus PET/CT+IMNS staging, respectively. Receipt of IMNS did not correlate with any outcome on either univariate or multivariate analysis (p>0.05). Patterns of failure in both groups were similar, including crude isolated nodal failure rates (8% PET/CT-only versus 14% PET+IMNS group, p=0.202). CONCLUSIONS: Patients undergoing IMNS had similar survival and patterns of recurrence as those receiving PET/CT alone. Further study, ideally prospectively, is needed to determine which subgroups might benefit from IMNS.

Practice Patterns of Thoracic Radiotherapy for Extensive-Stage Small-Cell Lung Cancer: Survey of US Academic Thoracic Radiation Oncologists.

PURPOSE: Despite the recent CREST trial demonstrating a survival benefit to thoracic radiotherapy (TRT) for patients with extensive-stage small-cell lung cancer (ES-SCLC) with response to chemotherapy, as well as endorsement by current National Comprehensive Cancer Network guidelines, TRT may not be uniformly delivered in clinical practice across all circumstances. METHODS AND MATERIALS: We surveyed US academic thoracic radiation oncologists regarding their practice patterns for TRT and assessed conditions in which withholding TRT could be warranted. A 27-question survey of demographics and practice patterns, including 5 clinical cases, was sent to 111 physicians. RESULTS: Response rate was 39% (43/111). Among respondents, 60% have at least 6 years of work experience following residency; 77% and 71% respectively see > 50 lung cancer and > 11 SCLC cases annually. Regarding practice patterns, 74% use TRT in 26% to 75% of patients with ES-SCLC. Respondents would withhold TRT in cases with Eastern Cooperative Oncology Group performance status ≥ 3 (91%), when pulmonary function necessitates continuous oxygen via nasal cannula (62%), for postchemotherapy tumor progression (58%), and if > 4 postchemotherapy extrathoracic metastases were present (58%). The 5 clinical cases highlighted practice variability, although 1 case had 100% agreement among respondents. CONCLUSIONS: Despite support of TRT administration from the CREST trial, there are several conditions associated with frequently withholding TRT. The most common reasons include performance status, postchemotherapy extent of disease, and pulmonary function; age and prechemotherapy extent of disease were least associated. Further research should aim to identify which subgroups of ES-SCLC benefit most from TRT.