The case for radiosurgery for brainstem metastases.

PURPOSE: To challenge the prevalent pessimism regarding the outcome of patients with metastases in the brainstem resulting in the use of whole brain radiation for palliation rather than stereotactic radiosurgery for definitive control and preservation of quality of life. We present our single institution review of the efficacy and safety of treating brainstem metastases aggressively with GKRS. METHODS: Forty-one patients with 45 total lesions treated with GKRS were included. Mean age was 58.7 years, ranging from 22 to 82. Tumor volumes were objectively calculated, treatment effects assessed on imaging and clinical data collected and correlated to the radiosurgical response. RESULTS: Mean survival after diagnosis of BSM was 11.6 months, ranging from 1.4 to 58.8 months. Margin dose ranged from 12 to 20 Gy. At first follow up, 11 (27%) patients had complete resolution of the treated lesion. At the second follow up 15 (37%) and third follow up 19 (46%) patients had a complete response. On average, there was a 64% decrease in tumor size at first follow up after treatment. 25 (61%) patients received WBRT in addition to radiosurgery; 16 (39%) received radiosurgery alone. There was no difference in overall survival between the two groups (p = 0.1324). ARE was seen in one patient who received  16 Gy to the margin of a 2.06 cm3 pontine tumor, but without correlative symptoms. One patient was treated with Bevacizumab® for progressive, but asymptomatic, edema following treatment that was not controlled by corticosteroids. CONCLUSIONS: Location in brainstem should not be a deterrent to the use of radiosurgery for these patients. The addition or exclusion of WBRT should be based on the clinical progression of the patient and within the limits of this study does not seem to impact overall survival. With improved survival as a result of better systemic therapy, these patients can benefit from better preservation of cognitive function by this strategy.

Comparison of single- and five-fraction schedules of stereotactic body radiation therapy for central lung tumours: a single institution experience.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is a treatment option for patients with early-stage non-small cell lung cancer who are medically inoperable or decline surgery. Here we compare the outcome of patients with centrally located lung tumours who underwent either single fraction (SF)- or five-fraction (FF-) SBRT at a single institution over 5 years. METHODS: Between January 2009 and October 2014, patients with centrally located lung tumours who underwent SBRT were included in this study. Data were retrospectively collected using an institutional review board-approved database. For analysis, the Kaplan-Meier method and competing risks method were used. RESULTS: In total, 11 patients received 26-30 Gy in 1 fraction, whereas 31 patients received 50-60 Gy (median 55 Gy) in 5 fractions. After a median follow-up of 12 months for SF-SBRT and 17 months for FF-SBRT groups (p = 0.64), 1-year overall survival rates were 82 and 87%, respectively. SF- and FF-SBRT groups showed no significant difference in grade 3+ toxicity (p = 0·28). The only grade 4 toxicity (n = 1) was reported in the SF-SBRT group. All toxicities occurred >12 months after the SBRT. CONCLUSIONS: SF- and FF-SBRT have comparable overall survival. SF-SBRT may have some utility for patients unable to have multi-fraction SBRT.

The dose penumbra of a custom-made shield used in hemibody skin electron irradiation.

We report our technique for hemibody skin electron irradiation with a custom-made plywood shield. The technique is similar to our clinical total skin electron irradiation (TSEI), performed with a six-pair dual field (Stanford technique) at an extended source-to-skin distance (SSD) of 377 cm, with the addition of a plywood shield placed at 50 cm from the patient. The shield is made of three layers of stan-dard 5/8'' thick plywood (total thickness of 4.75 cm) that are clamped securely on an adjustable-height stand. Gafchromic EBT3 films were used in assessing the shield's transmission factor and the extent of the dose penumbra region for two different shield-phantom gaps. The shield transmission factor was found to be about 10%. The width of the penumbra (80%-to-20% dose falloff) was measured to be 12 cm for a 50 cm shield-phantom gap, and reduced slightly to 10 cm for a 35 cm shield-phantom gap. In vivo dosimetry of a real case confirmed the expected shielded area dose.

Intravenous fluids for pain management in head and neck cancer patients undergoing chemoradiation.

BACKGROUND: Pain due to oral mucositis affects the majority of patients receiving chemoradiation (CRT) for head and neck cancer (HNC), and often results in dehydration. Anecdotally, intravenous (IV) fluids administered during treatment for the resultant dehydration was found to alleviate this pain. The purpose of this retrospective study was to evaluate the effectiveness of IV fluids as a method pain management in this patient population. METHODS: Patients with oral mucositis pain, secondary to CRT for HNC, were given IV fluids according to standard clinic protocol. Patients were evaluated using orthostatic vital signs and prospectively surveyed pre- and post-IV fluid administration, which included the Visual Analog Scale (VAS) for pain. Difference in pain pre- and post-IV fluid administration was evaluated using a two-tailed paired Student's t-test. RESULTS: Twenty-four patients with a total of 31 fluid administrations was available for analysis. Twenty-three patients were receiving or had recently completed CRT. One patient was receiving radiation alone. Six instances of fluid administration were excluded due to: refusal to complete the survey, concurrent pulmonary embolism, concurrent pain medication, and drug seeking behavior. Average pain score decreased from 6.5 [standard deviation (SD) 2.1] prior to IV fluids to 4.0 (SD 2.4) following fluid administration (P<0.001). CONCLUSIONS: To our knowledge, this is the first report directly correlating IV fluid administration with pain relief, even in the absence of orthostasis. Our findings indicate that in patients undergoing CRT for HNC, the use of IV fluids alone was effective in acutely and significantly reducing pain secondary to oral mucositis.

Two- Versus Four-Times Weekly Acupuncture-Like Transcutaneous Electrical Nerve Stimulation for Treatment of Radiation-Induced Xerostomia: A Pilot Study.

Background: Xerostomia occurs in the majority of patients undergoing chemoradiation therapy for head and neck cancer (HNC). Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) treatment has been studied as an encouraging modality to improve salivary function and related symptoms. The purpose of this study was to compare ALTENS treatment by using a four-times weekly schedule for 6 weeks versus a twice-weekly schedule for 12 weeks with a validated xerostomia scale at 15 months from the start of ALTENS treatment. Materials and Methods: This single-center randomized study was conducted in 30 patients treated with radiotherapy with or without chemotherapy for HNC between 2014 and 2017, who had at least grade 1 or 2 symptomatic dry mouth (xerostomia) according to CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0). These patients were randomly assigned to receive ALTENS four-times weekly for 6 weeks or two-times weekly for 12 weeks. The University of Michigan 15-item Xerostomia-related Quality of Life Scale (XeQoLS) was administered at 6, 9, 15, and 21 months from the start of ALTENS treatment. A random-effects generalized linear model was used to model the overall XeQoLS score at the 15-month endpoint; adjusted for a random time effect, a fixed treatment arm, and interaction of time and treatment. Comparison between arms was based on a 0.05 nominal significance level. Results: XeQoLS decreased for all patients (although not statistically for each arm) from a mean of 22 and 21 at baseline (in the four times per week and twice weekly arms) to 12 in both arms at 15 months, with no difference between arms (p = 0.68). There were no attributable grade 1-3 adverse events. Arms were balanced for age, gender, race, and baseline xerostomia. Conclusions: This study demonstrates that both ALTENS regimens are safe, well tolerated, and appear to be equally effective. We now routinely make ALTENS units available for home use.

Total Skin Electron Beam Therapy for Mycosis Fungoides Revisited With Adjuvant Systemic Therapy.

BACKGROUND: Although standard-dose total skin electron beam therapy (TSEBT) has been thought to provide the greatest clinical benefit for mycosis fungoides, recent studies have shown that low-dose TSEBT may also provide high rates of disease control. MATERIALS AND METHODS: A retrospective chart review was conducted for patients receiving TSEBT for mycosis fungoides at a single institution from 2009 to 2017. Patients were evaluated for overall survival, progression-free survival, and duration of clinical benefit. Partial response was defined as any documented clinical regression of lesions, whereas complete response was defined as complete resolution of lesions. RESULTS: Twenty patients were included in the study. Twelve patients received low-dose radiation (≤ 12 Gy), and 8 received standard-dose radiation (> 12 Gy). Response rate was 100% in both groups. The rate of complete response was 38% in the standard-dose group and 25% in the low-dose group. There was no difference in overall survival between the 2 groups (P = .84). There was also no difference in median progression-free survival (P = .95) or duration of clinical benefit (P = .95) between the 2 groups. Of low-dose patients, 33% received immediate systemic therapy, whereas 92% received adjuvant topical or systemic therapy. In the standard-dose group, only 25% received systemic adjuvant therapy, and 63% received adjuvant topical or systemic therapy. CONCLUSION: Low-dose TSEBT with adjuvant therapy results in adequate symptom palliation, comparable to standard-dose TSEBT. Low-dose TSEBT should be considered a standard treatment option in this population.

Long-term outcomes of interventions for radiation-induced xerostomia: A review.

Xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for reduction of xerostomia burden vary widely, with options including: sialagogue medications, saliva substitutes, acupuncture, vitamins, hyperbaric oxygen, submandibular gland transfer, and acupuncture or associated treatments. In this review, we sought to evaluate long-term outcomes of patients treated with various interventions for radiation-induced xerostomia. A literature search was performed using the terms "xerostomia" and "radiation" or "radiotherapy"; all prospective clinical trials were evaluated, and only studies that reported 1 year follow up were included. The search results yielded 2193 studies, 1977 of which were in English. Of those, 304 were clinical trials or clinical studies. After abstract review, 23 trials were included in the review evaluating the following treatment modalities: pilocarpine (three); cevimeline (one); amifostine (eleven); submandibular gland transfer (five); acupuncture like transcutaneous electrical nerve stimulation (ALTENS) (one); hyperbaric oxygen (one); and acupuncture (one). Pilocarpine, cevimeline, and amifostine have been shown in some studies to improve xerostomia outcomes, at the cost of toxicity. ALTENS has similar efficacy with fewer side effects. Submandibular gland transfer is effective but requires an elective surgery, and thus may not always be appropriate or practical. The use of intensity-modulated radiation therapy, in addition to dose de-escalation in select patients, may result in fewer patients with late xerostomia, reducing the need for additional interventions.

Stereotactic body radiation therapy for non-small cell lung cancer: A review.

Stereotactic body radiation therapy (SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer (NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility, prescription dose and delivery, and follow up duration varied widely. Three-years overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.

Genetic variation in total number and locations of GnRH neurons identified using in situ hybridization in a wild-source population.

The evolution of brain function in the regulation of physiology may depend in part upon the numbers and locations of neurons. Wild populations of rodents contain natural genetic variation in the inhibition of reproduction by winter-like short photoperiod, and it has been hypothesized that this functional variation might be due in part to heritable variation in the numbers or location of gonadotropin releasing hormone (GnRH) neurons. A naturally variable wild-source population of white-footed mice was used to develop lines artificially selected for or against mature gonads in short, winter-like photoperiods. We compared a selection line that is reproductively inhibited in short photoperiod (Responsive) to a line that is weakly inhibited by short photoperiod (Nonresponsive) for differences in counts of neurons identified using in situ hybridization for GnRH mRNA. There was no effect of photoperiod, but there were 60% more GnRH neurons in total in the Nonresponsive selection line than the Responsive selection line. The lines differed specifically in numbers of GnRH neurons in more anterior regions, whereas numbers of GnRH neurons in posterior areas were not statistically different between lines. We compare these results to those of an earlier study that used immunohistochemical labeling for GnRH neurons. The results are consistent with the hypothesis that the selection lines and natural source population contain significant genetic variation in the number and location of GnRH neurons. The variation in GnRH neurons may contribute to functional variation in fertility that occurs in short photoperiods in the laboratory and in the wild source population in winter.