Cutaneous adnexal carcinomas (CAC) are rare neoplasms arising from hair follicles and sebaceous, apocrine, and eccrine glands. While in general prognosis is good, these tumors are thought to be locally aggressive. Due to the rare nature of these tumors, treatment paradigms have been adapted from skin cancer data. Tumors are generally treated with surgery, with some high-risk patients receiving adjuvant radiation. However, the role of radiation remains undefined and practice varies by institution. Here we aim to identify cohorts of patients that may be at higher risk and analyze outcomes. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with CAC with skin as the primary site. Patients diagnosed between 1998 and 2010 were included. Patients with known metastatic disease were excluded. Five-year cause-specific survival (CSS) was then calculated for multiple variables, including tumor size, nodal status, subsite, age, sex, race, and grade. Grade was divided into low grade (I and II) and high grade (III and IV). Frequency of radiation use was evaluated with regard to risk factors. A total of 3551 patients who met the above criteria were identified. The median age was 68 years, and 54.4% were male. Ethnicity was as follows: white 81.2%, black 6.1%, other 5.1%, and unknown 7.5%. Median follow-up was not reached. Grade, nodal status, and age were found to have statistically significant (11.4%, 23.0%, 4.6%, P<0.05) impacts on 5-year CSS. Patients with low- and high-grade disease were found to have 5-year CSS of 97.3% and 85.9%. Those who were node negative vs positive at presentation were noted to have 5-year CSS of 97.1% vs 74.1%. Last, patients stratified by age (70 years as cutoff) had 5-year CSS of 97.6% (<70) and 93.0% (≥70). In all, 7% of well-differentiated tumors and 18% of poorly differentiated tumors received radiation. Node-negative and node-positive patients received radiation in 5% and 58% of cases. While overall prognosis is good, we identified variables that were associated with a statistically inferior 5-year CSS. Nodal involvement and high tumor grade were most predictive, as noted in Table 1. Patients with these risk factors may derive benefit from comprehensive postoperative radiation as these tumors tend to be locoregionally aggressive. Despite its potential therapeutic value, our study shows radiation has been underutilized in these high-risk groups. While prospective data is the best way to confirm or refute our findings, it is always a major clinical challenge to conduct such a study in this rare set of tumors. Nevertheless, we need more data on other potential risk factors such as perineural invasion, extracapsular extension, and lymphovascular invasion.

Merkel cell carcinoma (MCC) is a rare neuroendocrine malignancy of the skin with a predilection for aggressive behavior. Previous studies evaluating sentinel lymph node biopsy (SLNB) in MCC have shown positivity rates typically ranging from 22% to 48% in clinically N0 patients. The benefit of SLNB has also been well established in other similarly aggressive tumors, such as melanoma. As a result, sentinel lymph node biopsy (SLNB) is currently recommended for all clinically N0 patients, though its impact remains unclear. The aim of this review was to evaluate for a survival benefit in clinically N0 patients undergoing SLNB. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with MCC from 2003 through 2012 with skin as the primary site. Patients up to age 75 years were included, provided they underwent a cancer-directed surgery. Patients with positive lymph nodes or distant disease were excluded. Cause-specific survival was then compared in patients who underwent SLNB as opposed to no pathologic nodal evaluation. A total of 603 patients were identified who met the above criteria. Patients undergoing SLNB had a median age of 65 years with a range of 38-75, 59% were male, and 95% were white. With regard to tumor size: 57% were ≤2 cm, 13% were 2-5 cm, and 30% were >5 cm. In all, 52% of patients received radiation. Patients with no pathologic nodal evaluation had a median age of 68 years with a range of 37-75, 60% were male, and 94% were white. With regard to tumor size, 34% were ≤2 cm, 19% were 2-5 cm, and 47% were >5 cm. A total of 48% of patients received radiation. Patients undergoing SLNB had an improved 5-year CSS of 91.3% (95% CI 86.4-94.5%) compared to the nonpathologic nodal evaluation group, with a 5-year CSS of 72.5% (95% CI 65.4-78.4%). When analyzing tumors ≤2cm, the improved outcome was maintained for SLNB patients vs nonpathologic the nodal evaluation group with a 5-year CSS of 94.70% (95% CI 88.4-97.6) compared to 79.3% (95% CI 66.6-87.6%). A CSS advantage was found for patients undergoing SLNB. This advantage remained significant when stratifying for tumors <2 cm. The reason for this advantage is not fully clear but could be in part from decreased false negatives for nodal staging, therapeutic effect of the SLNB, or a result of more complete care. While prospective data are needed to confirm these findings, the rare nature of these tumors renders this a clinical challenge. Regardless, our current findings support the standard of care of SLNB in clinically N0 patients.

Normal tissue sparing strategies are becoming the standard for modern radiation therapy; without organ preservation the toxicity associated with external beam radiation therapy, such as xerostomia, adversely affects a patient’s long-term quality of life (QOL). Recently, clinicians have come to understand that there are significant changes to the head and neck (H&N) anatomic compartments induced by radiation therapy, despite efforts to spare normal structures. Herein, we propose an investigation of the anatomic and volume changes of the major salivary (parotid and submandibular) glands during treatment with concurrent chemoradiation. We further assess the volume changes of the deep and superficial parotid glands during our IMRT treatment. Our ultimate goal is to identify the timing at which radiation-induced changes to the salivary glands occur, the effects on saliva quality, and assess QOL, with the future goal to design an adaptive radiation therapy paradigm to maximize the quality of life of H&N patients. We retrospectively investigated 20 patients with recurrent or newly diagnosed squamous cell carcinoma of the H&N carcinoma treated with concurrent chemoradiation therapy. Assessed, were the volume and anatomic positions of the parotid and submandibular glands at the time of CT simulation, the 12th, 25th, and final fraction of image guided radiation therapy. We compared the total gland volumes, and then measured position translation to a bony reference (C2 dens). We utilized the embedded volume, distance, and dosing tools within the treatment planning software package. Cohort median age was 61 (3:1 male:female ratio). Fifteen patients were diagnosed with stage IVa H&N squamous cell carcinoma. There was a balance of left vs. right-sided disease. Patients received a minimum of 66 Gy, with a median dose of 70 Gy. Mean treatment package time was 44d; 85% of patients received concurrent chemotherapy. Median weight loss was 7.4%. CCRT vs. no chemotherapy resulted in a trend towards significant mean parotid gland volume loss (41.9 ± 19.4% vs. 35.2 ± 20.1%; P = 0.18). Volume loss was greatest by the first 12 fractions of treatment. For submandibular glands, our sample small sample size suggested a trend increased volume loss with CCRT. The glands exhibited a medial displacement of 5-8mm during the course of treatment. No differences in unstimulated/stimulated saliva output or pH were seen between the two groups. Our data suggests a connection with use of CCRT and salivary gland changes. Due to a small sample size, these differences were not statistically significant, however, we are increasing our study size in light of this important result. We wish to identify timing of gland changes, dose effect on saliva chemistry, and assess QOL to design an adaptive CCRT paradigm to maximize QOL.

Inflammatory breast cancer (IBC) is an aggressive subtype of breast cancer. The current treatment paradigm is trimodality approach with neoadjuvant chemotherapy, modified radical mastectomy (MRM), and post-mastectomy radiation therapy (PMRT). Advancements in systemic therapy have improved survival increasing the importance of locoregional control. Even with improving outcomes, survival rates remain unsatisfactory prompting the need to identify individuals that may benefit from treatment intensification. We report tumor characteristics, patient demographics, and oncologic outcomes of IBC in the modern era in order to identify subgroups with poor outcomes. We searched the Surveillance, Epidemiology, and End Results (SEER) database for women with breast cancer. This cohort was narrowed to women with non-metastatic [Adjusted AJCC 6th M (1988+) M0] IBC [Adjusted AJCC 6thT (1988+) T4d] with MRM [(1998+) Breast] with or without external beam PMRT. To be included, patients were treated with either ipsilateral MRM with or without reconstruction with the specified race, age, hormone receptor [ER/PR Status], grade, nodal stage [(1988+)], marital, and radiation data. A minimum of 5 years of follow-up was required. We report the actuarial 5-year cause-specific survival. We identified a cohort of 4841 women treated between 1998 and 2007. The median age of diagnosis was 55. The actuarial 5-year CSS for the whole cohort was 56% (95% CI; 54.0-57.2). Black women made up 13% while white women, other races, and unknown represented 81%, 6%, and <1% respectively. Blacks, whites, and other had 5-year CSS of 42% (37.3-46.0), 58% (55.8-59.3), and 59% (51.8-64.9) respectively. Blacks had a statistically significant (SS) lower CSS than the other groups. PMRT (n = 2903) had a SS benefit compared to no RT (n = 1439) with 5-year CSS of 59% (57.3-61.3) and 49% (46.7-52.4) respectively. Women over 70 years of age had a SS lower CSS compared to women between 50-69, but not when compared to ages 20-49. Patients with high-grade histology had a SS lower CSS than intermediate and low-risk patients with CSS of 49% (47-51.8), 68% (64.6-70.8), and 82% (71.6-89.1) respectively. Negative hormone receptor status or being divorced/widowed was also associated with SS worse survival compared to receptor positive disease and being married respectively. Our study confirms that IBC has several tumor factors are associated with worse survival and suggests some patient factors are associated with health disparity. As such, select patients (e.g. black women) may benefit from individualized treatment intensification including additional adjuvant systemic therapy and/or dose escalated PMRT. Select patients may also benefit from more intense post-treatment surveillance and support. Long-term follow-up and prospective data, if feasible, is needed to confirm our findings and conclusions.

To study the dosimetric effect of Qfix kVue Calypso-compatible couch top and rails for spine stereotactic body radiation therapy (SBRT) patients treated with intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques. The computed tomography (CT) dataset for Qfix kVue Calypso-compatible couch top with rails were imported into the treatment planning system (TPS). Ten patients who underwent spine SBRT at our institution were selected for this study. The patients were treated initially on a stereotactic linear accelerator without the couch being part of the dose calculation. Eight patients were treated with static IMRT posterior fields and 2 patients were treated using the VMAT technique. Couch top and rails were added to the structures as support devices and the dose was recalculated for (a) couch top and rails (CR) (b) couch-top and no rails (CNR), then the results were compared the results to no couch-top no-rails (NCNR). Dose covering 100% of the target volume (D100%), dose covering 99% of the target volume (D99%), dose covering 95% of the target volume (D95%), dose covering 90% of the target volume (D90%), volume receiving 100% of the prescription dose (V100%), conformal index (CI), dose gradient index (DGI), and spinal cord threshold and maximum doses were compared to the initial plan with NCNR. The average D100% was 77.89% ± 11.78%, 74.51% ± 12.24%, and 75.83 ± 12.67% for NCNR, CR, CNR (p=0.84), respectively. The average D99% was 91.64% ± 9.57%, 89.93% ± 9.48%, and 91.15% ± 9.55% for NCNR, CR, CNR (p=0.98), respectively. The average D95% was 99.14% ± 9.96%, 95.23% ± 9.76, and 96.78% ± 9.84% for NCNR, CR, CNR (p=0.047), respectively. The average D90% was 101.3% ± 0.65%, 97.11% ± 2.48, and 98.75% ± 2.12% for NCNR, CR, CNR (p=0.0004), respectively. The maximum dose to the spinal cord was 1750.79 ± 41.84, 1672.90 ± 40.90, and 1709.91 ± 41.35 for NCNR, CR, CNR (p=0.97), respectively. In all cases, the spinal cord threshold dose was far below the tolerances and the differences were insignificant. Average CI was 1.18 ± 0.16, 0.53 ± 0.39, and 0.86 ± 0.24 for NCNR, CR, CNR (p=0.0002), respectively. The Qfix kVue Calypso-compatible couch top has a significant impact on the target coverage. The impact was higher with the IMRT technique and with the rails. Even with no rails, target coverage can be significant so it is highly recommended to include the couch top in the plan and move the rails out of the way.

Hodgkin’s lymphoma (HL) is a curable form of pediatric cancer. Late effects from treatment are a concern. Radiation therapy (RT) can be associated with toxicity, including secondary malignant neoplasms (SMN). Pediatric protocols have attempted to decrease RT dose or eliminate RT due to toxicity. Here we evaluate characteristics associated with utilization of RT for pediatric HL, their effects on outcomes and development of SMN. The SEER database was queried for patients diagnosed with HL at ages 0-19 years from 1973-2012. Patient factors were assessed in regards to utilization of RT. Cause specific (CSS) and overall survival (OS) were calculated. Observed-to-expected ratios (O/E) were calculated for secondary tumor sites, comparing the development of cancer to incidence rates for the general population. P<0.05 was used to determine significance. 6572 patients were identified. 83.8% of patients were white, 52.4% male, and 54.7% of patients received RT. Use of RT decreased by decade from 71.5% between 1973 and 1979, 62.7% in the 1980s, 52.1% in the 1990s, to 49.9% in patients treated after 2010. The lowest yearly rate was 39.1% in 2012. RT use increased with age; 35% for those under 4, 50.3% from 5-9 years, 55.5% for those 10-19 years. No difference existed in RT use by sex (males 55.2% vs females 54.2%). Black patients (49.3%) were less likely to receive RT compared to whites (52.9%) and others (52.2%). 90% of patients were from metropolitan areas, with no difference in delivery of RT in metropolitan areas (54.8%) vs nonmetropolitan areas (54.4%). 332 SMNs (O/E 5.87) occurred. RT patients developed 240 SMNs (O/E 6.50) compared with 81 SMNs (O/E 4.81) in patients without RT (P<0.05). RT patients had higher rates of salivary gland, digestive, respiratory, soft tissue, breast, and hematologic cancers compared to patients not receiving RT. Females were at higher risk for all SMNs and solid tumors. For the entire cohort, 10 year CSS and OS were significantly improved for those treated with RT (92.7%, 90.6%) compared to those who did not receive RT (90%, 87.3%). By decade, CSS and OS were significantly improved in RT patients in the 1970s and 1980s. OS and CSS were also improved in the RT cohort in the 1990s and 2000s, though not significantly. Six hundred thirteen patients died from cancer, including 451 from HL and 162 from SMNs. The next leading cause of death was diseases of the heart (76). Use of radiation therapy for pediatric Hodgkin’s lymphoma has decreased over time. A benefit to CSS and OS for patients treated with radiation is present regardless of decade of diagnosis. Improved chemotherapy and increased OS in HL has diminished this relative difference to the point it is no longer significant. SMN is the second leading cause of mortality in this cohort and is more common in females treated with RT.

Inflammatory breast cancer (IBC) is an uncommon but aggressive variant. The current treatment paradigm is trimodality therapy with neoadjuvant chemotherapy, modified radical mastectomy (MRM), and post-mastectomy radiation therapy (PMRT). As systemic therapy decreases rates of distant metastatic disease and improves survival, the need for long-term locoregional control has become more essential. We hypothesize select subgroups benefit relatively less from conventional PMRT. We report the benefit of RT on oncologic outcomes of IBC by subgroup to identify patients that may be suitable for individualized treatment intensification. We searched the Surveillance, Epidemiology, and End Results (SEER) database for women with breast cancer. This cohort was narrowed to women with non-metastatic [Adjusted AJCC 6th M (1988+) M0] IBC [Adjusted AJCC 6th T (1988+) T4d] with MRM [(1998+) Breast] with or without external beam PMRT. To be included, patients were treated with either ipsilateral MRM with or without reconstruction with the specified race, age, hormone receptor [ER/PR Status], grade, nodal stage [Adjusted AJCC 6th N (1988+)], and radiation data. Our primary endpoint was actuarial 5-year cause-specific survival (CSS). We identified a cohort of 4841 women treated between 1998 and 2007. The median age of diagnosis was 55. Black and white women comprised 13% and 81% of the cohort respectively. The actuarial 5-year CSS for the whole cohort was 56%. PMRT (n = 2903) was utilized in 67% of patients while 33% received no RT. There was a significant benefit of PMRT compared to no RT with 5-year CSS of 59% and 50% respectively (Table 1). The benefit was not statistically significant (SS) in black women, but was in white women. N0, N1, N2, and N3 patients comprised 12%, 33%, 27%, and 28% of the cohort respectively. Node negative women had no CSS benefit at 5 years, but node positive women had a significant benefit of RT regardless of nodal stage. Low, intermediate, and high-grade tumors made up 2%, 27%, and 71% of the group. PMRT provided a significant CSS benefit in high-grade tumors with a trend in benefit in the intermediate group. Women over 70 years of age had a significantly lower CSS compared to women between 50-69, but not when compared to ages 20-49. A SS benefit of PMRT was seen regardless of age, but the greatest benefit was seen in the 20-49 group (59% v 47%). Our study suggests select subgroups have worse survival and may benefit relatively less from conventional PMRT. As such, select patients may benefit from individualized treatment intensification including dose escalated PMRT and/or additional adjuvant systemic therapy. Further prospective data, if feasible, is needed to confirm our findings and conclusions.Tabled 1Abstract 2099; Table 1.PatientsSubgroupPMRTn=5-year CSS (95% CI)Whole Cohortn/aAll484156% (54.0-57.2)PMRT290359% (57.3-61.3)No143950% (46.7-52.4)RaceBlackPMRT36046% (39.4-51.3)No20235% (27.6-42.1)WhitePMRT236261% (59.0-63.5)No114352% (48.2-54.7) Open table in a new tab

Glioblastoma (GBM) and anaplastic astrocytoma (AA) are rare pediatric malignancies. These tumors are often treated with radiation therapy (RT), which can increase the risk for second malignant neoplasms (SMNs). These tumors can also be associated with genetic predisposition syndromes that increase the risk of secondary malignancy. The risk of second neoplasm in pediatric patients with AA or GBM has not been defined. The SEER database was queried to identify patients under age 19 at diagnosis of glioblastoma (ICD-O-3 9440/3) or anaplastic astrocytoma (ICD-O-3 9401/3). Population demographics were assessed. Cause specific (CSS) and overall survival were calculated. A MP-SIR session was utilized to determine secondary. Observed-to-expected ratios (O/E) were calculated with a 2-month latency period and with a latency period of 5 years to evaluate for early and late SMNs in comparison to incidence ratios for the population as a whole. P<0.05 was used to determine statistical significance. 478 patients with anaplastic astrocytoma and 668 patients with glioblastoma were identified. A majority of patients were white (n=885, 77.2%) and male (n=651, 56.8%). 17.2% of patients were diagnosed before age 5; 58.1% were diagnosed after age 10. 822 patients received surgery. 69.4% of AAs and 74.5% of GBMs were treated with radiation. At 60 months, CSS and OS for AA were 40.8% and 39.0%, and for GBM were 19.6%, and 18.2%. Ninety-three percent of all deaths were attributed to primary cancer. Combined, AA and GBM had significantly increased development of SMN (O/E 10.26) and solid tumors alone (O/E 11.55). Compared to GBM, patients diagnosed with AA had higher incidences of all SMN (O/E 13.44 vs 7.97) and solid tumors (O/E 15.95 vs 8.58). The rates of CNS tumors and bone and joint tumors were all increased for the combined (O/E 56.79 and 63.83), AA (O/E 70.98 and 55.68), and GBM (O/E 40.57 and 74.79) cohorts, respectively. The combined cohort also had significantly elevated rates of leukemia and colon cancer. Patients treated with RT accounted for all of the increase risk of brain tumors, bone and joint tumors, colon cancer, and leukemia, with normal rates experienced in patients who were not treated with RT. With a latency period of 5 years, the risk of SMN (O/E 5.19), solid tumor (O/E 6.26), and brain tumors (O/E 61.17) remained elevated in those treated with RT, with normalized risk in patients not treated with RT. Pediatric patients with AA and GBM are at a higher risk of developing SMNs if treated with RT. Risk is higher in patients with AA, though this could be due to improved survival and more at risk years. As survival improves with novel therapies, SMNs will become more significant in patients with high grade glial tumors.

Stereotactic radiosurgery (SRS) is a treatment modality for classic trigeminal neuralgia (cTN). The success of SRS in facilitating long term pain control (LTPC) and minimizing facial numbness (FN) is dependent on maximizing prescribed dose (PD) to the trigeminal nerve and minimizing PD to the brain stem (BS). We analyzed several internationally standardized SRS treatment parameters and assessed as a primary endpoint whether either of them would predict LTPC. Our secondary endpoint assessed the role of BS pertinent treatment parameters in FN risk. We hypothesized that higher energy and homogeneity indexes independently decrease the risk of treatment failure. Between 2007 and 2015, 178 cTN patients underwent Stereotactic Radiosurgery (SRS), with a 4 millimeter collimator. Pain outcomes were obtained in 100 of these patients. Pain before and after SRS was scored as level I-V per the Barrow Neurological Institute (BNI) pain intensity scoring criteria. Pain relief was graded as an improvement to BNI levels I, II, or III from pre-SRS BNI levels IV or V. Treatment failure (TF) was graded as a return to BNI levels IV or V or need for additional SRS or operative intervention. Time to TF (TTF) and FN (TFN) were measured. The energy index, conformity index, homogeneity index (HI) [(D2% minus D98%)/D50%], and gradient index were calculated. BS D1CC, V10, and VB20 (volume receiving 20% of PD) were also assessed for purposes of secondary endpoint analysis. A statistical model using Cox regression evaluating our primary endpoint was designed comparing all TF and non-TF patients to determine TF risk. A similar model evaluating our secondary endpoint was designed comparing patients with and without FN to determine FN risk. Median PD was 80 Gy [range (r): 70-80]. The median follow-up was 15 months (r: 1.5-82). The median time to initial response was 1 month (r: 0.05-5) and the median TTF was 20 months (r: 0-82). Ninety percent reported initial pain relief, and actuarial rates of freedom from TF at 12, 24, 36, and 48 months were 55, 40, 33, and 28%, respectively. Statistical modeling showed that HI was the only treatment parameter that independently predicted time to TF (P = 0.0273). Each unit increase in HI had an 88.3% decrease in TF risk (HR = 0.117; 95% CI = 0.017-0.788). BS D1CC, V10, or VB20 did not predict FN. This is the first cTN series to suggest that optimization of the HI may enhance freedom from treatment failure and LTPC. Although this is a preliminary analysis, incorporation of the HI in treatment planning may be used to guide future SRS dosimetry in the treatment of cTN.