Disease and toxicity outcomes for a modern cohort of patients with squamous cell carcinoma of cutaneous origin involving the parotid gland: Comparison of volumetric modulated arc therapy and pencil beam scanning proton therapy.

OBJECTIVES: We sought to describe outcomes for locally advanced cutaneous squamous cell carcinoma (SCC) involving the parotid treated with volumetric modulated arc therapy (VMAT) versus pencil beam scanning proton beam therapy (PBT). MATERIALS AND METHODS: Patients were gathered from 2016 to 2022 from 5 sites of a large academic RT department; included patients were treated with RT and had parotid involvement by: direct extension of a cutaneous primary, parotid regional spread from a previously or contemporaneously resected but geographically separate cutaneous primary, or else primary parotid SCC (with a cutaneous primary ostensibly occult). Acute toxicities were provider-reported (CTCAE v5.0) and graded at each on treatment visit. Statistical analyses were conducted. RESULTS: Median follow-up was 12.9 months (1.3 - 72.8); 67 patients were included. Positive margins/extranodal extension were present in 34 cases; gross disease in 17. RT types: 39 (58.2 %) VMAT and 28 (41.8 %) PBT. Concurrent systemic therapy was delivered in 10 (14.9 %) patients. There were 17 treatment failures (25.4 %), median time of 168 days. Pathologically positive neck nodes were associated with locoregional recurrence (p = 0.015). Oral cavity, pharyngeal constrictor, and contralateral parotid doses were all significantly lower for PBT. Median weight change was -3.8 kg (-14.1 - 5.1) for VMAT and -3 kg (-16.8 - 3) for PBT (p = 0.013). Lower rates of ≥ grade 1 xerostomia (p = 0.002) and ≥ grade 1 dysguesia (p < 0.001) were demonstrated with PBT. CONCLUSIONS: Cutaneous SCC involving the parotid can be an aggressive clinical entity despite modern multimodal therapy. PBT offers significantly lower dose to organs at risk compared to VMAT, which seemingly yields diminished acute toxicities.

A multi-center analysis of single-fraction versus hypofractionated stereotactic radiosurgery for the treatment of brain metastasis.

BACKGROUND: Hypofractionated-SRS (HF-SRS) may allow for improved local control and a reduced risk of radiation necrosis compared to single-fraction-SRS (SF-SRS). However, data comparing these two treatment approaches are limited. The purpose of this study was to compare clinical outcomes between SF-SRS versus HF-SRS across our multi-center academic network. METHODS: Patients treated with SF-SRS or HF-SRS for brain metastasis from 2013 to 2018 across 5 radiation oncology centers were retrospectively reviewed. SF-SRS dosing was standardized, whereas HF-SRS dosing regimens were variable. The co-primary endpoints of local control and radiation necrosis were estimated using the Kaplan Meier method. Multivariate analysis using Cox proportional hazards modeling was performed to evaluate the impact of select independent variables on the outcomes of interest. Propensity score adjustments were used to reduce the effects confounding variables. To assess dose response for HF-SRS, Biologic Effective Dose (BED) assuming an α/ß of 10 (BED10) was used as a surrogate for total dose. RESULTS: One-hundred and fifty six patients with 335 brain metastasis treated with SF-SRS (n = 222 lesions) or HF-SRS (n = 113 lesions) were included. Prior whole brain radiation was given in 33% (n = 74) and 34% (n = 38) of lesions treated with SF-SRS and HF-SRS, respectively (p = 0.30). After a median follow up time of 12 months in each cohort, the adjusted 1-year rate of local control and incidence of radiation necrosis was 91% (95% CI 86-96%) and 85% (95% CI 75-95%) (p = 0.26) and 10% (95% CI 5-15%) and 7% (95% CI 0.1-14%) (p = 0.73) for SF-SRS and HF-SRS, respectively. For lesions > 2 cm, the adjusted 1 year local control was 97% (95% CI 84-100%) for SF-SRS and 64% (95% CI 43-85%) for HF-SRS (p = 0.06). On multivariate analysis, SRS fractionation was not associated with local control and only size ≤2 cm was associated with a decreased risk of developing radiation necrosis (HR 0.21; 95% CI 0.07-0.58, p < 0.01). For HF-SRS, 1 year local control was 100% for lesions treated with a BED10 ≥ 50 compared to 77% (95% CI 65-88%) for lesions that received a BED10 < 50 (p = 0.09). CONCLUSIONS: In this comparison study of dose fractionation for the treatment of brain metastases, there was no difference in local control or radiation necrosis between HF-SRS and SF-SRS. For HF-SRS, a BED10 ≥ 50 may improve local control.

Risk factors and management of oligometastatic non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is an aggressive malignancy with close to half of all patients presenting with metastatic disease. A proportion of these patients with limited metastatic disease, termed oligometastatic disease, have been shown to benefit from a definitive treatment approach. Synchronous and metachronous presentation of oligometastatic disease have prognostic significance, with current belief that metachronous disease is more favorable. Surgical excision of intracranial and extracranial oligometastatic disease has been shown to improve survival, especially in patients with lymph node-negative disease, adenocarcinoma histology and smaller thoracic tumors. Definitive radiation to sites of oligometastatic disease and initial thoracic disease has also been shown to have a similar impact on survival for both intracranial and extracranial disease. Recent studies have reported on the use of targeted agents combined with ablative doses of radiation in the oligometastatic setting with promising outcomes. In this review, we present the historical and current literature describing surgical and radiation treatment options for patients with oligometastatic NSCLC.

Does Certificate of Need Minimize Intensity Modulated Radiation Therapy Use in Patients with Low Risk Prostate Cancer?

PURPOSE: Certificate of Need (CON) laws are optional from state to state, and are meant to limit proliferation of certain unnecessary medical facilities. Theoretically, CON should limit the use of IMRT (intensity modulated radiation therapy) in the population who likely would benefit from it the least: older or debilitated men with low risk prostate cancer. We evaluated the effect of CON on IMRT use in these patients in a population-based cohort. METHODS AND MATERIALS: Using the Surveillance, Epidemiology and End Results (SEER) database linked with Medicare files, we identified male residents of SEER regions who were diagnosed in 2004-2009 with low- risk prostate cancer (T1, Gleason≤6, PSA<10) and were either ≥70 years old or ≥65 years old with Charlson comorbidity score ≥ 2. The endpoint was percentage of newly diagnosed patients who were treated with IMRT within 12 month of cancer diagnosis. Logistic regression was used to assess the impact of CON laws on IMRT use. RESULTS: Over 37% (4,491) of the patients came from states with radiation oncology CON laws, whereas 63% (7,572) came from non-CON states. IMRT was performed on 30% of CON patients versus 28% of non-CON patients. Logistic regression analysis revealed that IMRT was utilized more often in CON states than in non-CON states, odds ratio (OR) 1.13 (95% CI 1.04-1.23, p=0.006). CONCLUSIONS: CON laws do not effectively limit use of IMRT in older or debilitated patients with low risk prostate cancer.

Non-operative therapies for colorectal liver metastases.

Locoregional therapies for colorectal liver metastases complement systemic therapy by providing an opportunity for local control of hepatic spread. The armamentarium for liver-directed therapy includes ablative therapies, embolization, and stereotactic body radiation therapy. At this time, prospective studies comparing these modalities are limited and decision-making relies on a multidisciplinary approach for optimal patient management. Herein, we describe multiple therapeutic non-surgical procedures and an overview of the results of these treatments.

Treatment of recurrent metastatic head and neck cancer: focus on cetuximab.

EGFR belongs to the ErbB family of receptor tyrosine kinases and is associated with worse prognosis in head and neck squamous cell carcinoma (HNSCC). Cetuximab is a monoclonal antibody to the extracellular domain of EGFR and inhibits its downstream actions via multiple mechanisms. Besides its proven efficacy in locally advanced and incurable HNSCC, cetuximab has the distinct advantage of having a relatively tolerable side effect profile and not potentiating radiation toxicity. Though therapies for advanced HNSCC are evolving, locoregional recurrence and/or distant metastases occur in a large percentage of patients. Though some patients can be salvaged with surgery or radiation therapy, the majority are incurable, and are treated palliatively with systemic therapy. In the setting of first line therapy for recurrent/metastatic HNSCC, the EXTREME trial provided level 1 evidence that cetuximab improves overall survival when combined with cisplatinum and 5 FU. Following progression on first line chemotherapy, several phase II trials suggest that cetuximab monotherapy is a reasonable choice in this setting. Future studies should concentrate on clinical and molecular markers that may allow more personalized approaches to treating HNSCC, and combining EGFR inhibitors with other agents in a synergistic approach.

Efficacy of fiducial marker-based image-guided radiation therapy in prostate tomotherapy and potential dose coverage improvement using a patient positioning optimization method.

PURPOSE: To evaluate the dose coverage efficacy of fiducial marker-based prostate tomotherapy and a positioning correction optimization technique for the improvement of suboptimal dose distributions. METHODS: Three gold fiducial markers were implanted in prostate glands for patients who were to receive prostate tomotherapy. TomoTherapy megavoltage computed tomographies (MVCTs; TomoTherapy, Madison, WI) were routinely acquired at treatment and were registered to corresponding planning CTs based on the markers to correct for interfractional positioning deviations using translational table movements. The prostate glands and seminal vesicles were delineated on the MVCTs acquired for 10 patients at different treatment fractions and the treatment dose coverage was computed with the marker-based correction taken into account. The treatment dose coverage was compared with the corresponding plan to evaluate the efficacy of the marker-based image-guided radiation therapy (IGRT) approach. Separately, a hill-climbing optimization algorithm was used to optimize the positioning by maximizing a dose-based objective function. During the optimization, the dose was constantly recomputed with the translational correction until an optimized dose coverage was reached. This optimized dose coverage was compared with the marker-based dose coverage to evaluate dosimetric improvement for treatments in which suboptimal dose distributions were observed after the marker-based corrections. RESULTS: Suboptimal dose coverage of prostate glands and seminal vesicles were observed in about 8 and 6 of a total 75 fractions, respectively, after the marker-based IGRT positioning corrections. Six of the 10 patients experienced 1 or more factions of suboptimal prostate gland coverage and 2 of the 10 patients experienced 1 or more fractions of suboptimal seminal vesicle dose coverage. Utilization of the proposed positioning correction optimization method led to satisfactory dose coverage of both prostate glands and seminal vesicles for all 10 patients. CONCLUSIONS: Given the planning target volume margin size specified in the current study, the fiducial marker-based IGRT approach may not be completely adequate to achieve desired dose coverage of the target volumes at every fraction. Due to relatively poor image quality of MVCTs, additional investigations may be required to confirm the finding. The proposed positioning correction optimization method is shown to effectively improve the observed suboptimal dose coverage of the target volumes.

Mediator of DNA damage checkpoint protein 1 (MDC1) expression as a prognostic marker for nodal recurrence in early-stage breast cancer patients treated with breast-conserving surgery and radiation therapy.

The mediator of DNA damage checkpoint protein 1 (MDC1) regulates cell cycle checkpoints and recruits repair proteins to sites of double-stranded DNA damage using its BRCA1 carboxy-terminal (BRCT) domains. MDC1 under-expression has been associated with radiosensitivity in cells. The purpose of this study was to evaluate the clinico-pathologic and prognostic significance of MDC1 expression in a cohort of early-stage breast cancer patients treated with breast conservation therapy. Paraffin specimens from 489 women with early-stage breast cancer treated with breast conservation therapy were constructed into tissue microarrays. The arrays were stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and MDC1. This was correlated with clinico-pathologic factors and outcomes. MDC1 expression was evaluable in 351 cases (72%). Decreased MDC1 expression was found to be correlated with nodal failure (P = 0.05), but not ipsilateral breast relapse-free survival (IBRFS), distant metastasis-free survival (DMFS), or overall survival (OS). Subset analysis in node-negative patients revealed that decreased MDC1 expression predicted for nodal failure (P < 0.01). Our study is the first to assess the clinico-pathologic and prognostic significance of MDC1 expression in patients with early-stage breast cancer treated with lumpectomy and radiotherapy. MDC1 under-expression predicted for nodal failure, but not for IBRFS, DM, or OS. The role of other proteins involved in the DNA damage repair pathway and their effects on MDC1 expression, as well as the level of MDC1 expression in patients with BRCA1 mutations warrant further investigation.

The future of radiation oncology in the United States from 2010 to 2020: will supply keep pace with demand?

PURPOSE: Prior studies forecasted an incipient shortage of medical oncologists as a result of the aging US population, but the radiation oncology workforce has not been studied. Accordingly, we projected demand for radiation therapy and supply of radiation oncologists in 2010 and 2020 to determine whether a similar shortage may exist for this specialty. METHODS: Demand for radiation therapy in 2010 and 2020 was estimated by multiplying current radiation utilization rates (as calculated with Surveillance, Epidemiology, and End Results data) by population projections from the Census Bureau. Supply of radiation oncologists was projected using data from the American Board of Radiology inclusive of current radiation oncologists and active residents, accounting for variation in full-time equivalent status and expected survival by age and sex. RESULTS: Between 2010 and 2020, the total number of patients receiving radiation therapy during their initial treatment course is expected to increase by 22%, from 470,000 per year to 575,000 per year. In contrast, assuming that the current graduation rate of 140 residents per year remains constant, the number of full-time equivalent radiation oncologists is expected to increase by only 2%, from 3,943 to 4,022. The size of residency training classes for the years 2014 to 2019 would have to double to 280 residents per year in order for growth in supply of radiation oncologists to equal expected growth in demand. CONCLUSION: Demand for radiation therapy is expected to grow 10 times faster than supply between 2010 and 2020. Research is needed to explore strategies to enhance capacity to deliver quality radiation therapy despite increased patient loads.