Radiation therapy is an important tool in the care of patients with breast cancer.Today's breast cancer clinical trials demonstrate the volumetric-based strategies for contouring breast and regional lymph node targets and normal tissue can be common threads as well as points of differentiation.In this paper, we review approaches for contouring targets in breast cancer clinical trials to help site investigators effectively treat targets and meet normal tissue constraints.

Due to space requirements and a substantial financial burden, the feasibility of health systems adopting proton therapy has been called into question. However, advances in facility design and treatment delivery have allowed institutions offering proton therapy to reduce footprint while incorporating technological improvements at reduced costs. As the number of centers and patients treated continue to increase, this chapter will review the layout and interface of proton therapy facilities providing a detailed overview of the design, costs and faculty and staff considerations.

Cancer remains a significant medical challenge for modern health care. Therapies have improved. Chemotherapy can now be applied and targeted to specific expression products and biomarkers. Radiation therapy is directed to specific targets with applied image guidance including less normal tissue in the treatment fields. Surgery has improved with robotics and improvements in rehabilitation and recovery. More patients are surviving their primary challenge from malignancy. As such, more patients now have the imprint of therapy upon their normal tissues. It is important for all practitioners, including primary care physicians and medical subspecialists, to participate in the aftercare of these patients with a comprehensive strategic manner to both prevent normal tissue injury and ameliorate injury if/when it occurs.

This chapter details the history of radiation therapy, identifies essential components to a modern department of radiation therapy, and focuses on salient areas of improvement in patient outcome for the next generation of cancer patients. Tumor is more sensitive to radiation in an oxygenated environment; therefore a larger oxygen component to the tumor microenvironment should have a direct positive effect on tumor cell kill. The science of radiation biology continues to expand as radiation therapy continues to increase in demand as a patient care option. Brachytherapy can be used as a sole modality of care for patients with low risk factors for recurrence and as part of an integrated care plan combined with external radiation therapy for patients with intermediate and high risk features for tumor recurrence. Radiosurgery and stereotactic radiation therapy are important areas of research as cell kill from high dose therapy may be exceptionally proficient.

To investigate the interrelation between economic, marital, and known histopathologic/therapeutic prognostic factors in presentation and survival of patients with lung cancer in nine different ethnic groups. A retrospective review of the SEER database was conducted through the years 2007–2012. Population differences were assessed via chi‐square testing. Multivariable analyses (MVA) were used to detect overall survival (OS) differences in the total population (TP, N = 153,027) and for those patients presenting with Stage IV (N = 70,968). Compared to Whites, Blacks were more likely to present with younger age, male sex, lower income, no insurance, single/widowed partnership, less squamous cell carcinomas, and advanced stage; and experience less definitive surgery, lower OS, and lung cancer‐specific (LCSS) survival. White Hispanics presented with younger age, higher income, lower rates of insurance, single/widowed partnership status, advanced stage, more adenocarcinomas, and lower rates of definitive surgery, but no difference in OS and LCSS than Whites. In the TP and Stage IV populations, MVAs revealed that OS was better or equivalent to Whites for all other ethnic groups and was positively associated with insurance, marriage, and higher income. Blacks presented with more advanced disease and were more likely to succumb to lung cancer, but when adjusted for prognostic factors, they had a better OS in the TP compared to Whites. Disparities in income, marital status, and insurance rather than race affect OS of patients with lung cancer. Because of their presentation with advanced disease, Black and Hispanics are likely to have increased benefit from lung cancer screening.

Craniopharyngioma is a rare tumor that is expected to occur in ∼400 patients/year in the United States. While surgical resection is considered to be the primary treatment when a patient presents with a craniopharyngioma, only 30% of such tumors present in locations that permit complete resection. Radiotherapy has been used as both primary and adjuvant therapy in the treatment of craniopharyngiomas for over 50 years. Modern radiotherapeutic techniques, via the use of CT-based treatment planning and MRI fusion, have permitted tighter treatment volumes that allow for better tumor control while limiting complications. Modern radiotherapeutic series have shown high control rates with lower doses than traditionally used in the two-dimensional treatment era. Intracavitary radiotherapy with radio-isotopes and stereotactic radiosurgery may have a role in the treatment of recurrent cystic and solid recurrences, respectively. Recently, due to the exclusive expression of the Beta-catenin clonal mutations and the exclusive expression of BRAF V600E clonal mutations in the overwhelming majority of adamantinomatous and papillary tumors respectively, it is felt that inhibitors of each pathway may play a role in the future treatment of these rare tumors.

To report our experience with stereotactic radiosurgery (SRS) for brain metastases from lung cancer primaries and assess the prognostic significance of post-SRS systemic therapy (PSST) given various clinical predictors including systemic disease status (SDS). In this single-institution retrospective study, we analyzed 96 patients with lung cancer and ECOG PS≤2 who underwent LINAC-based SRS for 183 brain metastases between 2007 and 2013. Patients underwent metastectomy (24%), whole brain radiation (WBRT) (12%), or both (5%) prior to SRS while 48% received PSST with a median duration of 2 months (1-19). The SDS at SRS was recorded; 57% of patients had only pulmonary disease (1 or both lungs with adjacent nodal involvement) while 43% had distant extrapulmonary disease. The median age of the cohort was 65 (41-85), and 55% was male. Histologies included adenocarcinoma (60%), squamous cell carcinoma (13%), small cell (6%), poorly differentiated (16%), and other histologies (5%). Dates of primary diagnosis, first CNS disease, and PSST initiation were recorded. For analysis, the SRS-PSST interval (SPI) was divided into ≤30 days and >30 days. Cox regression analyses as well as log-rank tests were performed. At a median follow-up of 5 months (1-59), the median survival was 5.8 months and the actuarial overall survival at 3, 6, 12, 24, and 36 months was 75%, 48%, 29%, 13%, and 5%, respectively. Negative predictors for survival were older age (HR 1.03, 95% CI 1.00-1.06, P=.029) and extrapulmonary disease (HR 2.30, 95% CI 1.34-3.96, P=.003), while the addition of PSST positively predicted for survival (HR 0.46, 95% CI 0.29-0.75, P=.002). Gender, metastectomy or WBRT prior to SRS, and the primary-to-CNS disease diagnosis interval were not significant. In patients receiving PSST, positive predictors for survival were SSI>30 days (HR 0.24, 95% CI 0.11-0.53, P=.0005) and longer PSST duration (HR 0.91, 95% CI 0.84-0.98, P=.016) regardless of SDS. Log-rank test revealed no survival difference between histologies. Our results suggest the prognostic significance of PSST. While a longer duration of PSST was found to be beneficial, delaying its initiation to >30 days after SRS was also found to be prognostic regardless of SDS at SRS. This latter finding was potentially influenced by pre-SRS systemic therapy or neurotoxicity after SRS. Further investigation is warranted to define the optimal SPI.

OBJECTIVE: Meningeal melanocytomas are rare entities that range from benign and well-differentiated lesions with a favorable prognosis to higher-grade lesions that may undergo malignant transformation with subsequent CNS dissemination. Transition from a meningeal melanocytoma to primary CNS melanoma is particularly rare with only a handful of cases reported. Systemic spread of a transformed meningeal melanocytoma, an exquisitely rare occurrence, is, to the best of our knowledge, reported in only three cases. Here we report the case of a woman who initially presented with multifocal meningeal melanocytomas with subsequent rapid transformation, diffuse CNS seeding, and systemic metastases. CLINICAL PRESENTATION AND MANAGEMENT: A 43 year-old woman presented with headaches, nausea, and vomiting for two months with negative GI work-up. She experienced a syncopal episode with CT and MRI brain scans showing 3 dural-based lesions involving the foramen magnum, fourth ventricle, and right CPA. The patient underwent STR of the lesions; the anterior lesion was inaccessible. Pathology reported a melanocytoma with malignant features. A negative dermatology and ophthalmology work-up were performed. The patient received post-operative radiotherapy (50.4 Gy) to the posterior fossa. Six months following surgery she presented with new neurological symptoms, and MRI of the neuroaxis showed new leptomeningeal enhancement within the cerebellum, thoracic spine, and supratentorially. With neuro-oncology input, she was started on Temodar and underwent palliative spinal RT. Unfortunately she continued to experience pain, and follow-up MRI showed new intrathecal C-spine nodules. Abdominal imaging revealed multiple lung and liver metastases, with biopsy of a 7-cm liver lesion revealing malignant melanoma. The patient unfortunately continued to deteriorate and succumbed to her disease approximately 9 months following diagnosis. CONCLUSION: Meningeal melanocytomas are rare tumors that are not only challenging to diagnose, but challenging to clinically predict and manage. This case illustrates these challenges and the multidisciplinary response needed to optimize outcomes.

Purpose/Objective(s)HIV patients (pts) have longer life spans and more intact immune systems after the discovery of HAART. The purpose of this study is to report radiation therapy (RT) outcomes and toxicity in pts with squamous cell carcinoma of the head and neck (SCCHN) and co-existing HIV.Materials/MethodsThis study is a retrospective analysis of pts treated at our center between the years 2005 and 2012. Fifteen pts with SCCHN and HIV were eligible to our study. The male pts were 53% and the median age was 58 years (range, 48-68 years). All pts listed their ethnicity as African American (AA), Hispanic (H), or others. The 15 pts consisted of 10 laryngeal cases, 4 oropharyngeal disease sites, and 1 sinus case. 13 were locally advanced with Stage III/IV disease, 1 was Stage II disease, and 1 was recurrent tumor. Only 5 (33.3%) had their tumors tested for HPV and only 1 was positive. All 15 pts were treated definitively with 6MV photon beams and IMRT to a median dose of 70 Gy. Weights, treatment times, CD4 counts, neutrophil counts, and viral loads (VLs) were documented.ResultsThe median follow-up was 21 months (range, 1.5-85 months). Eleven pts (73%) were on HAART at the time of RT. The median pre-treatment CD4 count was 320 (range, 36-966). Post-treatment median CD4 count fell to 73.5 (range, 15-278). 8/15 pts had undetectable pre-treatment VLs. The VLs for the others ranged between 243 and 102,531. Twelve pts (80%) received CCRT. Two (13%) tolerated reduced doses of chemotherapy and 6 (40%) required a reduced number of cycles. Eighty-seven percent experienced a nadir in their neutrophil counts during their RT+/-chemo with a median value of 1.3 (0.3-4.8, 4 cases of Grade III toxicity). All pts had a treatment break and missed between 1 and 29 days of RT (Median 4.0, Mean 9.0). Sixty percent of pts experienced a treatment break of more than 3 days. The total treatment period ranged from 46 - 92 days (Median 51.0, Mean 59.7). 3 pts had breaks due to neutropenia, 4 due to weight loss, 1 due to infection, 1 for mucositis, and the rest due to minor complaints. Nine pts experienced a greater than 20 lb weight loss (Median 23 pounds, range, 3.8-50) and 27% had RTOG Grade III weight loss. 3 pts received a PEG tube during their RT and 2 had PEG tubes inserted upfront. Seven pts (47%) experienced an RTOG Grade III side effect and 10 pts (67%) experienced an RTOG Grade II toxicity. Seven pts (6 laryngeal, 1 oropharynx) had recurrence of disease of which 3 were metastatic. The median time to recurrence was 6 months (1-12). Four pts died, 2 related to progression of their cancer. Pre-treatment VLs and CD4 counts did correlate with weight loss but not with length of treatment or outcome.ConclusionsThe analysis demonstrates that HIV+ pts with SCCHN experienced more toxicity during their RT and had poor treatment outcomes when compared with prior non-HIV studies. An emphasis should be placed on improved control of HIV, which the study suggests may increase tolerance to treatment. Purpose/Objective(s)HIV patients (pts) have longer life spans and more intact immune systems after the discovery of HAART. The purpose of this study is to report radiation therapy (RT) outcomes and toxicity in pts with squamous cell carcinoma of the head and neck (SCCHN) and co-existing HIV. HIV patients (pts) have longer life spans and more intact immune systems after the discovery of HAART. The purpose of this study is to report radiation therapy (RT) outcomes and toxicity in pts with squamous cell carcinoma of the head and neck (SCCHN) and co-existing HIV. Materials/MethodsThis study is a retrospective analysis of pts treated at our center between the years 2005 and 2012. Fifteen pts with SCCHN and HIV were eligible to our study. The male pts were 53% and the median age was 58 years (range, 48-68 years). All pts listed their ethnicity as African American (AA), Hispanic (H), or others. The 15 pts consisted of 10 laryngeal cases, 4 oropharyngeal disease sites, and 1 sinus case. 13 were locally advanced with Stage III/IV disease, 1 was Stage II disease, and 1 was recurrent tumor. Only 5 (33.3%) had their tumors tested for HPV and only 1 was positive. All 15 pts were treated definitively with 6MV photon beams and IMRT to a median dose of 70 Gy. Weights, treatment times, CD4 counts, neutrophil counts, and viral loads (VLs) were documented. This study is a retrospective analysis of pts treated at our center between the years 2005 and 2012. Fifteen pts with SCCHN and HIV were eligible to our study. The male pts were 53% and the median age was 58 years (range, 48-68 years). All pts listed their ethnicity as African American (AA), Hispanic (H), or others. The 15 pts consisted of 10 laryngeal cases, 4 oropharyngeal disease sites, and 1 sinus case. 13 were locally advanced with Stage III/IV disease, 1 was Stage II disease, and 1 was recurrent tumor. Only 5 (33.3%) had their tumors tested for HPV and only 1 was positive. All 15 pts were treated definitively with 6MV photon beams and IMRT to a median dose of 70 Gy. Weights, treatment times, CD4 counts, neutrophil counts, and viral loads (VLs) were documented. ResultsThe median follow-up was 21 months (range, 1.5-85 months). Eleven pts (73%) were on HAART at the time of RT. The median pre-treatment CD4 count was 320 (range, 36-966). Post-treatment median CD4 count fell to 73.5 (range, 15-278). 8/15 pts had undetectable pre-treatment VLs. The VLs for the others ranged between 243 and 102,531. Twelve pts (80%) received CCRT. Two (13%) tolerated reduced doses of chemotherapy and 6 (40%) required a reduced number of cycles. Eighty-seven percent experienced a nadir in their neutrophil counts during their RT+/-chemo with a median value of 1.3 (0.3-4.8, 4 cases of Grade III toxicity). All pts had a treatment break and missed between 1 and 29 days of RT (Median 4.0, Mean 9.0). Sixty percent of pts experienced a treatment break of more than 3 days. The total treatment period ranged from 46 - 92 days (Median 51.0, Mean 59.7). 3 pts had breaks due to neutropenia, 4 due to weight loss, 1 due to infection, 1 for mucositis, and the rest due to minor complaints. Nine pts experienced a greater than 20 lb weight loss (Median 23 pounds, range, 3.8-50) and 27% had RTOG Grade III weight loss. 3 pts received a PEG tube during their RT and 2 had PEG tubes inserted upfront. Seven pts (47%) experienced an RTOG Grade III side effect and 10 pts (67%) experienced an RTOG Grade II toxicity. Seven pts (6 laryngeal, 1 oropharynx) had recurrence of disease of which 3 were metastatic. The median time to recurrence was 6 months (1-12). Four pts died, 2 related to progression of their cancer. Pre-treatment VLs and CD4 counts did correlate with weight loss but not with length of treatment or outcome. The median follow-up was 21 months (range, 1.5-85 months). Eleven pts (73%) were on HAART at the time of RT. The median pre-treatment CD4 count was 320 (range, 36-966). Post-treatment median CD4 count fell to 73.5 (range, 15-278). 8/15 pts had undetectable pre-treatment VLs. The VLs for the others ranged between 243 and 102,531. Twelve pts (80%) received CCRT. Two (13%) tolerated reduced doses of chemotherapy and 6 (40%) required a reduced number of cycles. Eighty-seven percent experienced a nadir in their neutrophil counts during their RT+/-chemo with a median value of 1.3 (0.3-4.8, 4 cases of Grade III toxicity). All pts had a treatment break and missed between 1 and 29 days of RT (Median 4.0, Mean 9.0). Sixty percent of pts experienced a treatment break of more than 3 days. The total treatment period ranged from 46 - 92 days (Median 51.0, Mean 59.7). 3 pts had breaks due to neutropenia, 4 due to weight loss, 1 due to infection, 1 for mucositis, and the rest due to minor complaints. Nine pts experienced a greater than 20 lb weight loss (Median 23 pounds, range, 3.8-50) and 27% had RTOG Grade III weight loss. 3 pts received a PEG tube during their RT and 2 had PEG tubes inserted upfront. Seven pts (47%) experienced an RTOG Grade III side effect and 10 pts (67%) experienced an RTOG Grade II toxicity. Seven pts (6 laryngeal, 1 oropharynx) had recurrence of disease of which 3 were metastatic. The median time to recurrence was 6 months (1-12). Four pts died, 2 related to progression of their cancer. Pre-treatment VLs and CD4 counts did correlate with weight loss but not with length of treatment or outcome. ConclusionsThe analysis demonstrates that HIV+ pts with SCCHN experienced more toxicity during their RT and had poor treatment outcomes when compared with prior non-HIV studies. An emphasis should be placed on improved control of HIV, which the study suggests may increase tolerance to treatment. The analysis demonstrates that HIV+ pts with SCCHN experienced more toxicity during their RT and had poor treatment outcomes when compared with prior non-HIV studies. An emphasis should be placed on improved control of HIV, which the study suggests may increase tolerance to treatment.

AIM:To report long-term outcomes for HIV-positive patients who underwent radiation therapy (RT) for benign lymphoepithelial cysts (BLEC) of the parotid glands. PATIENTS AND METHODS:In this single institution retrospective study of HIV-associated BLEC of the parotids, the medical records of 37 HIV-positive patients who were treated with RT between 1987-2012 were reviewed. Patients were stratified into two groups; group A consisted of 15 patients (40.5%) who received a total dose of ≤18Gy, with a median dose 10 Gy (range 8-18Gy), and group B consisted of 22 patients (59.5%) who received a total dose of 24 Gy. In addition to dosing information, additional patient data were collected, including demographics, HAART compliance, follow-up, and re-treatment status. RESULTS:The median age at the time of treatment was 41 (range=7-70) years. With a median follow-up of 35 (range=12-75) months for the entire cohort, the complete response (CR) and partial response (PR) rates were 35% and 8%, respectively. All but one of 15 patients in Group A (lower total dose) eventually experienced local failure with the re-emergence of parotid hypertrophy. Among the patients in group B (higher total dose of 24 Gy), 55%, 13%, and 32% experienced CR, PR, and LF, respectively. Median times to failure in groups A and B were 7 and 20 months, respectively (p<0.0001). Similarly, logistic regression test revealed the higher dose to be associated with better response rate (i.e. CR or PR) (p<0.0001), which was also statistically significant (p=0.03) after adjusting for confounding variables (age, race, gender, HAART use, and fractionation). CONCLUSION:A total dose of 24 Gy continues to be recommended for durable cosmetic control of BLEC of the parotid glands that is associated with HIV-seropositivity.

To report 25 years of cosmetic outcome of radiation therapy (RT) of HIV patients with benign lymphoepithelial cysts (BLEC) of the parotid glands. This is a single institution retrospective study of seropositive HIV patients with BLEC. From January 1987-2012, 37 patients were eligible for our study. The whole parotid was treated with RT. Patients were stratified into 2 groups; Group A consisted of 15 patients (37.5%) who underwent RT dose of ≤18 Gy, median dose 10 Gy (range, 8-18 Gy) and group B consisted of 25 patients (62.5%) who underwent RT dose of 24. After a median follow-up of 35 months (range, 2-75) for the whole cohort, the actuarial overall response (OvR) was 44.4%. Specifically complete response (CR) and partial response (PR) were 36% and 8.4%, respectively. In group A 93% had local failure (LF). While in group B 54.5%, 13.7%, and 31.8% had CR, PR, and LF, respectively. Median time to failure in group A and B was 7 and 15 months, respectively. Chi-square test showed significant correlation between RT dose of 24 Gy (p < 0.01) and cosmetic control. Similarly, logistic regression test showed that 24 Gy is associated with better OvR (p < 0.01) and multiple regression analysis after adjusting all other confounding variables (e.g., age, race, gender, RT fractionation size, and BLEC duration) showed better OvR with 24 Gy (p = 0.03). Radiation therapy dose of 24 Gy is recommended for excellent and sustained cosmetic control of BLEC of the parotid glands in HIV patients.

Positron emission tomography (PET) has become a common practice for staging and planning of head and neck (H&N) cancer radiation treatments (RT). In our previous publication we have reported GTV-PET to be less than GTV-CT in 54% and greater in 23% patients. Whether PET is sufficient for GTV delineation is controversial. In this study we look at patterns of local failures in such patients. Two hundred fifty-two patients with locally advanced H&N cancers were treated at our center between 2005 and 2012 using PET-CT based planning. Thirty-one patients who experienced local failures were selected for review. Our practice is to Boolean the GTV (GTV-Total) derived from PET (GTV-PET) and CT (GTV-CT) and use that to create treatment volumes (CTV = GTV+0.5 cm and PTV = CTV+0.5 cm). Gross disease received 70 Gy and areas of microscopic disease received 54 Gy using IMRT-SIB technique. Area of Overlap (OVF) between the pretreatment volumes and recurrences (GTV-rec) were measured in order to conduct a comparative analysis. Of 252 patients planned with a pre-RT PET, 31 experienced local failures. The median time to tumor recurrence was 7 months (range, 2-30 months). Ten of 31 patients (32%) experienced both local and distant failures. The overlap areas between GTV-CT and GTV-PET ranged from 0.05-0.98 for CT (median 0.27) and 0.11-1.0 for PET (median 0.75). The median difference in volume between GTV-CT and GTV-PET was 20.8 cm3 (range, 2-224 cm3). The GTV-CT/GTV-rec OVF was greater than or equal to the GTV-PET/GTV-rec OVF in 26/31 cases (84%). The median GTV-CT/GTV-rec OVF was 0.42 (range, 0-1.0) and the median GTV-PET/GTV-rec OVF was 0.21 (range, 0-.89). The PTV-CT/GTV-rec OVF (median value of 0.97) was greater than or equal to the PTV-PET/GTV-rec OVF (median value of 0.82) in 27/31 cases (87%). Wilcoxon sign rank test was used to test the differences and these results were statistically significant. The GTV-rec was completely encompassed by PTV-Total (70 Gy) in 19 cases; 8 patients had recurrent disease extending from inside PTV-Total into the low dose region. 3 patients failed in the low dose region alone. GTV-rec extended outside the PTV-PET in 26/31 (84%) patients. CT remains the standard of care in delineating H&N tumor volumes and RT planning. Areas of gross disease on pre-treatment PET-CT do not correlate as well with areas of disease recurrence.