Feasibility and outcome of re-irradiation in the treatment of multiply recurrent pituitary adenomas.

PURPOSE: This study evaluates the toxicity and outcomes of re-irradiation to the sella for pituitary adenomas. METHODS: Patients diagnosed with a pituitary adenoma and treated with two or more courses of radiation treatment (RT) to the sella were retrospectively analyzed for: initial diagnosis, including histological type and functional status; RT modality, technique, dose, and fractionation; treatment with surgery, endocrine agents, and chemotherapy; toxicity of RT including radiation-induced optic neuropathy, radionecrosis, and radiation-induced neoplasms; and outcomes including local control, distant metastasis, biochemical control of functional tumors, and vital status at last follow-up. RESULTS: We identified 15 patients with non-functioning pituitary adenoma (n = 6), Cushing's disease (CD) (n = 5), acromegaly (n = 3), and prolactinoma (n = 1). Initial RT was delivered using opposed lateral fields in 8 (53%), intensity-modulated radiation therapy (IMRT) in 4 (27%), fractionated stereotactic radiation therapy (FSRT) in 1 (6.7%), and stereotactic radiosurgery (SRS) in 2. The median dose was 49.5 Gy for fractionated RT and 15-25 Gy for SRS. Re-irradiation was performed a median of 5.8 years after initial RT, and delivered using lateral opposed beams (n = 1), IMRT (n = 4), linear-accelerator based SRS (n = 3), FSRT (n = 3), gamma knife surgery (n = 2), and yttrium-90 brachytherapy (n = 1). The median dose of re-irradiation was 45 Gy (range 27.9-54 Gy) for fractionated RT and 18 Gy for SRS. Radiation-induced optic neuropathy (RION) was observed in 2 (13.3%) patients, 6 months and 14 years after re-irradiation; the 5-year rate of RION was 9 %. Temporal lobe necrosis (TLN) occurred in two patients (13.3%), both of whom had received SRS. The 2- and 5-year rates of TLN were 10 and 28%. Actuarial local control rates at 2 and 5 years were 80 and 58%, respectively. Biochemical remission occurred in one of three patients with CD. Four patients (27%) ultimately developed pituitary carcinoma. CONCLUSIONS: Re-irradiation is a feasible treatment option for local control in patients with recalcitrant pituitary adenomas, with acceptable rates of RION and TLN given the lack of options that may be available otherwise. Re-irradiation, however, did not control hormonal hypersecretion.

Peptide receptor radionuclide therapy implementation and results in a predominantly gastrointestinal neuroendocrine tumor population: A two-year experience in a nonuniversity setting.

ABSTRACT: Neuroendocrine tumors (NETs) are rare, but the incidence and prevalence of NETs are increasing in the United States. While surgery is the preferred treatment for NETs, it is not a viable option for metastatic disease. Lutathera (177Lu-DOTATATE) is approved by the United States Food and Drug Administration and the European Medicines Agency for the treatment of gastroenteropancreatic (GEP)-NETs in adults. There is limited information on GEP-NET treatment responses to Lutathera.Our institution launched a peptide receptor radionuclide therapy (PRRT) service line using Lutathera with involvement from a multidisciplinary team and complete collaboration between hospital administration and clinical providers. A prospective registry study was also established in order to collect patient demographics and clinical data regarding the treatment of GEP primary NETs with Lutathera.Between August 2018 and July 2020, 35 GEP-NET patients were treated with Lutathera, of which 65.71% received 4 complete cycles and 25.71% received 3 cycles; 5.71% and 2.86% received 2 and 1 cycles of PRRT, respectively. Most adverse events during the course of our study were low grade using the common terminology criteria for adverse events system. Of the patients who completed all 4 cycles: 22% showed partial response to Lutathera, 44% showed stable disease, and 13% showed disease progression based on a qualitative assessment of positron emission tomography/computed tomography imaging.From our experience, Lutathera was well tolerated in patients with GEP-NET. Additional studies are needed to examine long-term clinical and patient-reported outcomes associated with GEP-NET treatment as well as financial considerations for hospitals embarking on a PRRT program.

Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma.

BACKGROUND: This study was designed to evaluate the impact of tyrosine kinase inhibitors (TKIs) on incidence of brain metastasis (brain metastasis) and overall survival (OS) in patients with metastatic renal cell cancer (mRCC). METHODS: All patients who presented with mRCC but no brain metastasis in the intervals 2002 to 2003 and 2006 to 2007 were identified using the institutional tumor registry. The following data were collected: age, sex, Fuhrman grade, disease sites, nephrectomy, systemic therapy including TKIs (sorafenib or sunitinib), Memorial Sloan-Kettering Cancer Center risk category, brain metastasis treatment, and vital status. Statistical analysis was performed using the Cox proportional hazards model and the Kaplan-Meier method. RESULTS: Of the 338 patients who were identified; 154 (46%) were treated with a TKI before brain metastasis, and 184 (54%) were not. There were no significant differences in age, histology, nephrectomy, involved sites of disease other than lung, or Memorial Sloan-Kettering Cancer Center risk category between the groups. Median OS was longer in the TKI-treated group (25 months vs 12.1 months, P < .0001). In multivariate analysis, TKI treatment (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.38-0.74; P < .001) was associated with improved OS. Forty-four (13%) patients developed a brain metastasis, including 29 (15.8%) of the non-TKI group and 15 (9.7%) of the TKI group. The 5-year actuarial rate of brain metastasis was 40% versus 17%, respectively (P < .001). TKI treatment was associated with lower incidence of brain metastasis in Cox multivariate analysis (HR, 0.39; 95% CI, 0.21-0.73; P = .003). Lung metastasis increased the risk of brain metastasis (HR, 9.61; 95% CI, 2.97-31.1; P < .001). CONCLUSIONS: Treatment with TKI agents reduces the incidence of brain metastasis in mRCC. Lung metastasis is a risk factor for brain metastasis development.

Characteristics and outcome of radiation and chemotherapy-related mucoepidermoid carcinoma of the salivary glands.

BACKGROUND: Mucoepidermoid carcinoma (MEC) of the salivary glands has been reported to occur in patients previously treated with chemotherapy and/or radiation. The purpose of our study is to review the patient, tumor, and treatment characteristics of patients who develop a treatment-related MEC. PROCEDURE: A PubMed search of English language articles was performed using the keywords and MeSH terms: mucoepidermoid, salivary gland, radiation-induced, second malignancy, radiotherapy, and chemotherapy. RESULTS: The search yielded 23 articles describing 58 patients who received chemotherapy and/or radiotherapy (RT) and subsequently developed MEC. The most common initial diagnoses were acute lymphoblastic leukemia (n = 18), acne (n = 9), and Hodgkin lymphoma (n = 6). Patients were divided into three groups according to chemotherapy and RT treatment: chemotherapy alone (n = 14), RT alone (n = 14), or chemotherapy and RT (n = 30). The parotid gland was the most common site for secondary MEC. Latent time (LT) to development of MEC from initial tumor treatment was significantly shorter in the patients treated with chemotherapy ± RT versus RT alone (7.9 years vs. 27.2 years, P < 0.01). The most common treatment for MEC was surgery alone followed by surgery and postoperative RT. The 2- and 5-year overall survival rates were 98% and 93.4% while the 2- and 5-year locoregional control rates were 97.7% and 92.5%, respectively. There was no difference in survival or locoregional control between groups exposed to RT alone, chemotherapy alone, or chemotherapy with RT for the initial tumor. CONCLUSION: Radiation and chemotherapy-related MEC has an excellent prognosis.

Moral attitudes and beliefs among couples pursuing PGD for sex selection.

This article reports the results from a study of couples participating in a research protocol in which IVF/preimplantation genetic diagnosis (PGD) was available for non-medical sex selection. The study sought to characterize the moral attitudes and beliefs of couples actively pursuing IVF/PGD solely for purposes related to sex selection. Eighteen couples participated in ethnographic interviews from November 2005 to April 2006. These interviews explored couples' motivations for pursuing sex selection, moral beliefs and attitudes regarding sex selection and sources of moral ambivalence about the use of IVF/PGD for sex selection. Couples reported a combination of motivations for pursuing sex selection, including a desire to limit family size, concerns about parental age and financial concerns about multiple pregnancies. Many couples compared their decision to choices about abortion, maintaining that individuals have a right to make such decisions privately. Couples frequently expressed anxiety about telling their other children and family members about their plans to use IVF/PGD for sex selection. Few couples cited concerns about the physical or emotional burdens of IVF/PGD. The study's findings suggest that couples pursuing IVF/PGD for sex selection view this as an ethically complex decision and express considerable uncertainty about the ethical acceptability of this practice.

Outcomes of Patients With Metastatic Renal Cell Carcinoma and Bone Metastases in the Targeted Therapy Era.

BACKGROUND: Bone metastases (BMs) occur commonly in patients with metastatic renal cell carcinoma (mRCC). Tyrosine kinase inhibitors (TKIs) have improved the outcomes for patients with mRCC. However, data on the outcomes of mRCC patients with BMs treated with TKIs are limited. We describe the outcomes of patients with BMs treated with TKI therapy and compare them with the outcomes from a pre-TKI group. PATIENTS AND METHODS: Using an institutional tumor registry, a retrospective review of patients with mRCC from 2002 to 2003 and 2006 to 2007 was performed. The baseline characteristics were analyzed, and overall survival (OS) was estimated using the Kaplan-Meier method. The predictors of OS were analyzed using Cox regression analysis. RESULTS: The data from 375 patients were reviewed. Of these patients, 188 (50%) started treatment with TKIs and 187 (50%) had started treatment in the pre-TKI era. The distribution of patient characteristics was similar. The sites of organ metastases were equally distributed, including BMs in 48% of the patients in each cohort. The median OS for the patients treated in the TKI era was 22 months (95% confidence interval [CI], 17-25 months) compared with 14 months (95% CI, 10-19 months; P < .01) for the historical controls. A subset analysis of patients with BM in the TKI era demonstrated a median OS of 24 months (95% CI, 17-28 months) compared with 18 months (95% CI, 10-21 months; P < .01) in pre-TKI era. The predictors of shorter OS were a higher Memorial Sloan Kettering Cancer Center score; liver, lung, and brain metastases; and multiple sites of BMs (hazard ratio, 1.38; 95% CI, 1.02-1.91; P = .04). The rate of new BM development was the same in the pre- and post-TKI era. CONCLUSION: The rate of BM development was the same in the pre- and post-TKI era. The management of BMs in patients with mRCC remains challenging.

New Strategies for Multimodality Therapy in Treating Locally Advanced Cervix Cancer.

Cervical cancer is the fourth most common cause of cancer of women worldwide. In the developing world, it comprises 12% of all cancers of women. Since 1999, the mainstay of treatment for locally advanced cervical cancer (LACC) has been concurrent cisplatin-based chemoradiation. However, outcomes in this disease remain suboptimal, with long-term progression-free survival and overall survival rates of approximately 60%. There are several new strategies of combined modality treatment under evaluation in LACC, including chemotherapy before and after treatment as well as novel agents such as poly-adenosine diphosphate ribose polymerase inhibitors, antiangiogenic blockage, and immunotherapy. We provide a brief overview of these strategies and their potential in the treatment of women with LACC.

Comparison of supine and prone craniospinal irradiation in children with medulloblastoma.

PURPOSE: To compare port film rejection and treatment outcome according to craniospinal irradiation (CSI) position for medulloblastoma. METHODS AND MATERIALS: We retrospectively searched for patients ≤19 years treated with CSI for medulloblastoma at 1 department. We collected the following data: age; sex; risk group; need for general anesthesia; radiation therapy (RT) dose and fractionation; and the acceptance or rejection of weekly port films during treatment. We also collected data on outcomes, including neuraxis recurrence and possible complications such as myelitis. RESULTS: Of 46 children identified, 23 were treated prone (median age, 8.1 years) and 23 supine (median age, 7.2 years). High-risk disease was seen in 26% of prone and 35% of supine patients (P = .25). There was no difference in use of general anesthesia between those treated prone versus supine (57% vs 61%). The rejection rate of cranial port films in the prone position was 35%, which was significantly higher than the rate of 8% in patients treated supine (P < .0001). The 5-year progression-free (P = .37) and overall survival (P = .18) rates were 62% and 67% for prone and 76% and 84% for supine patients. There were no isolated junctional failures or radiation myelitis in either CSI position. CONCLUSIONS: The supine position for CSI was found to have similar survival outcomes compared with the prone position. A higher proportion of rejected cranial port films was seen in children treated in the prone position.

Dosimetric predictors of duodenal toxicity after intensity modulated radiation therapy for treatment of the para-aortic nodes in gynecologic cancer.

PURPOSE: To determine the incidence of duodenal toxicity in patients receiving intensity modulated radiation therapy (IMRT) for treatment of para-aortic nodes and to identify dosimetric parameters predictive of late duodenal toxicity. METHODS AND MATERIALS: We identified 105 eligible patients with gynecologic malignancies who were treated with IMRT for gross metastatic disease in the para-aortic nodes from January 1, 2005, through December 31, 2009. Patients were treated to a nodal clinical target volume to 45 to 50.4 Gy with a boost to 60 to 66 Gy. The duodenum was contoured, and dosimetric data were exported for analysis. Duodenal toxicity was scored according to Radiation Therapy Oncology Group criteria. Univariate Cox proportional hazards analysis and recursive partitioning analysis were used to determine associations between dosimetric variables and time to toxicity and to identify the optimal threshold that separated patients according to risk of toxicity. RESULTS: Nine of the 105 patients experienced grade 2 to grade 5 duodenal toxicity, confirmed by endoscopy in all cases. The 3-year actuarial rate of any duodenal toxicity was 11.7%. A larger volume of the duodenum receiving 55 Gy (V55) was associated with higher rates of duodenal toxicity. The 3-year actuarial rates of duodenal toxicity with V55 above and below 15 cm(3) were 48.6% and 7.4%, respectively (P<.01). In Cox univariate analysis of dosimetric variables, V55 was associated with duodenal toxicity (P=.029). In recursive partitioning analysis, V55 less than 13.94% segregated all patients with duodenal toxicity. CONCLUSIONS: Dose-escalated IMRT can safely and effectively treat para-aortic nodal disease in gynecologic malignancies, provided that care is taken to limit the dose to the duodenum to reduce the risk of late duodenal toxicity. Limiting V55 to below 15 cm(3) may reduce the risk of duodenal complications. In cases where the treatment cannot be delivered within these constraints, consideration should be given to other treatment approaches such as resection or initial chemotherapy.

The impact of tyrosine kinase inhibitors on the multimodality treatment of brain metastases from renal cell carcinoma.

OBJECTIVES: This study evaluated the effect of tyrosine kinase inhibitors (TKIs) on the brain metastasis (BM), local control (LC), and overall survival (OS) of patients with renal cell carcinoma (RCC) with BM. METHODS: A retrospective review of patients with RCC BM was conducted. Eligible patients from 2 eras: pre-TKI, 2002 to 2003 and post-TKI, 2006 to 2007, were identified. Prognostic factors, use, and type of systemic therapy were noted. The timing, number, size, and treatment modality data for each BM were recorded. Use of TKI and BM treatment modality were correlated to LC and OS. RESULTS: Eighty-one patients with 216 BMs were identified. Thirty-seven patients had BM at diagnosis and the remaining 44 were found to have BM at a later point. Forty-one patients never received a TKI and the remaining 40 received TKIs. Stereotactic radiosurgery, surgery, whole brain radiotherapy, or no local brain treatment was used for 89, 19, 24, and 75 lesions, respectively. The median OS from BM diagnosis was 5.4 months for the whole group: 4.4 versus 6.71 months in the never-TKI versus TKI groups, respectively. Patients who received TKIs post-BM development had a median OS of 23.6 months versus 2.08 and 4.41 months for the patients who received TKIs pre-BM or never-TKI, respectively (P=0.0001). LC was statistically superior in lesions managed with surgery or stereotactic radiosurgery versus the no local therapy. CONCLUSIONS: In patients with RCC and BM, TKIs are associated with a trend of improved OS, but no significant improvement in LC of BM. They may provide a significant benefit to patients with BM with no prior TKI exposure.