Radiation Therapy is Associated with Improved Outcomes in Merkel Cell Carcinoma.

BACKGROUND: Following wide excision of Merkel cell carcinoma (MCC), postoperative radiation therapy (RT) is typically recommended. Controversy remains as to whether RT can be avoided in selected cases, such as those with negative margins. Additionally, there is evidence that RT can influence survival. METHODS: We included 171 patients treated for non-metastatic MCC from 1994 through 2012 at a single institution. Patients without pathologic nodal evaluation (clinical N0 disease) were excluded to reflect modern treatment practice. The endpoints included local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). RESULTS: Median follow-up was 33 months. Treatment with RT was associated with improved 3-year LC (91.2 vs. 76.9 %, respectively; p = 0.01), LRC (79.5 vs. 59.1 %; p = 0.004), DFS (57.0 vs. 30.2 %; p < 0.001), and OS (73 vs. 66 %; p = 0.02), and was associated with improved 3-year DSS among node-positive patients (76.2 vs. 48.1 %; p = 0.035), but not node-negative patients (90.1 vs. 80.8 %; p = 0.79). On multivariate analysis, RT was associated with improved LC [hazard ratio (HR) 0.18, 95 % confidence interval (CI) 0.07-0.46; p < 0.001], LRC (HR 0.28, 95 % CI 0.14-0.56; p < 0.001), DFS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001), OS (HR 0.53, 95 % CI 0.31-0.93; p = 0.03), and DSS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001). Patients with negative margins had significant improvements in 3-year LC (90.1 vs. 75.4 %; p < 0.001) with RT. Deaths not attributable to MCC were relatively evenly distributed between the RT and no RT groups (28.5 and 29.3 % of patients, respectively). CONCLUSIONS: RT for MCC was associated with improved LRC and survival. RT appeared to be beneficial regardless of margin status.

LINAC-based stereotactic radiosurgery to the brain with concurrent vemurafenib for melanoma metastases.

While selective BRAF inhibitors have demonstrated improved outcomes in patients with metastatic BRAF V600E mutant melanoma, management of brain metastases prior to and during therapy presents challenges. Stereotactic radiosurgery (SRS) is an effective treatment for melanoma brain metastases, but there is limited safety and efficacy data on the use of SRS during BRAF therapy. An analysis was performed of patients with metastatic melanoma and brain metastases treated with SRS while on vemurafenib. MRI scans were reviewed post-SRS to evaluate local control (LC) as well as distant control. We identified 80 metastatic melanoma brain lesions treated in 24 patients. The median planning target volume was 0.28 cm(3) (range 0.05-4.19 cm(3)), and lesions were treated to a median dose of 24 Gy (range 15-24 Gy). The median follow up was 5.1 months (range 2-25.2 months). Eight (10 %) lesions showed progression at a median of 6.1 months (range 2-20.1 months) following SRS. Kaplan-Meier LC estimates at 6 and 12 months were 92 and 75 %, respectively. Fourteen (58 %) patients were noted to have distant brain failure at a median of 3.4 months (range 1.9-16.1 months) following treatment with SRS. Median overall (OS) from the date of SRS was 7.2 months (range 1.5-26.8 months) with a median of 11.9 months (range 1.5-28.5 months) since the date of brain metastases diagnosis. There was no evidence of increased toxicity with the combination of SRS and vemurafenib. SRS to brain metastases appears to be both safe and effective for patients treated concurrently with BRAF inhibitors.

Radiotherapy influences local control in patients with desmoplastic melanoma.

BACKGROUND: Desmoplastic melanoma may have a high risk of local recurrence after wide excision. The authors hypothesized that adjuvant radiotherapy (RT) would improve local control in patients with desmoplastic melanoma, resulting in at least a 10% absolute decrease in local recurrence rate. METHODS: A total of 277 patients from 1989 through 2010 who were treated for nonmetastatic desmoplastic melanoma by surgery with or without adjuvant RT were reviewed. Clinicopathologic and treatment variables were assessed with regard to their role in local control. RESULTS: A total of 113 patients (40.8%) received adjuvant RT. After a median follow-up of 43.1 months, adjuvant RT was found to be independently associated with improved local control on multivariable analysis (hazards ratio, 0.15; 95% confidence interval, 0.06-0.39 [P<.001]). Among 35 patients with positive resection margins, 14% who received RT developed a local recurrence versus 54% who did not (P=.004). In patients with negative resection margins, there was a trend (P=.09) toward improved local control with RT. In patients with negative resection margins and traditionally high-risk features, including a head and neck tumor location, a Breslow depth >4 mm, or a Clark level V tumor, RT was found to significantly improve local control (P< .05). The data from the current study would suggest that patients who would be good candidates for omitting RT included those with negative resection margins, a Breslow depth ≤ 4 mm, and either no perineural invasion present or a non-head and neck tumor location. CONCLUSIONS: RT for desmoplastic melanoma was independently associated with improved local control. Patients with positive resection margins or deeper tumors appeared to benefit the most from RT, whereas selected low-risk patients can safely omit RT.

Fractionated stereotactic radiotherapy to the post-operative cavity for radioresistant and radiosensitive brain metastases.

Following surgical resection for brain metastases, fractionated stereotactic radiotherapy (FSRT) has been used as an alternative to single dose treatment for large cavities and to reduce risks of late toxicity. The purpose of this study was to evaluate the outcomes of patients treated with FSRT to the post-operative bed for both radioresistant and radiosensitive brain metastases. Between December 2009 and May 2013 a total of 65 patients with newly diagnosed brain metastases were treated with resection followed by FSRT. Patients were treated to a total dose of 20-30 Gy in five fractions. Median planning target volume (PTV) was 16.88 cm(3) (range 4.87-128.43 cm(3)). The median follow-up for all patients was 8.5 months (range 1.1-28.6 months) with a median of 12.9 months for living patients. One and two year Kaplan-Meier estimates of local control were 87.0 and 70.0 %, respectively. Local control at 1 year was 85.6 and 88.0% for radioresistant and radiosensitive tumors, respectively (p = 0.44). A PTV ≥17 cm(3), was associated with local failure, HR 8.63 ((1.44-164.78); p = 0.02). One and two year distant control rates were 50.9 and 46.2%, respectively with six patients (9.2%) experiencing leptomeningeal disease. OS rates at 1 and 2 years were 65.2 and 47.5%, respectively. Survival was significantly associated with recursive partitioning analysis class (p = 0.001) and graded prognostic assessment score (p = 0.005). One case of radionecrosis was noted on follow-up imaging. FSRT in five fractions offers excellent local control in both radiosensitive and radioresistant tumors with minimal toxicity.

Desmoplastic melanoma: is there a role for sentinel lymph node biopsy?

BACKGROUND: The utility of sentinel lymph node biopsy (SLNB) for desmoplastic melanoma (DM) is debated. We describe a large single-institution experience with SLNB for DM to determine clinicopathologic factors predictive of SLN metastasis. METHODS: Retrospective review identified 205 patients with DM who underwent SLNB from 1992 to 2010. Clinicopathologic characteristics were correlated with SLN status and outcome. RESULTS: Median age was 66 years, and 69 % of patients were male. Median Breslow thickness was 3.7 mm. In 128 cases (62 %), histologic subtype data was available; 61 cases (47.7 %) were mixed and 67 cases (52.3 %) were pure DM. A positive SLN was found in 28 cases (13.7 %); 24.6 % of mixed and 9 % of pure DM had SLN metastases. Multivariable analysis demonstrated that after controlling for age, histologic subtype correlated with SLN status [odds ratio: 3.0 for mixed vs pure, 95 % confidence interval: 1.1-8.7; p < .05]. Completion lymph node dissection was performed in 24 of 28 positive SLN patients with 16.7 % of cases having additional nodal disease. After a median follow-up of 6.3 years, 38 patients developed recurrence and 61 patients died. Positive SLN patients had a significantly higher risk of melanoma-related death compared with negative SLN patients (p = .01). CONCLUSIONS: The overall risk for SLN metastasis for DM is 13.7 % and is significantly higher for mixed (24.6 %) compared with pure (9.0 %) DM. We believe that these rates are sufficient to justify consideration of SLNB for both histologic variants, especially since detection of SLN disease appears to predict a higher risk for melanoma-related death.

Novel treatments for melanoma brain metastases.

BACKGROUND: The development of brain metastases is common in patients with melanoma and is associated with a poor prognosis. Treating patients with melanoma brain metastases (MBMs) is a major therapeutic challenge. Standard approaches with conventional chemotherapy are disappointing, while surgery and radiotherapy have improved outcomes. METHODS: In this article, we discuss the biology of MBMs, briefly outline current treatment approaches, and emphasize novel and emerging therapies for MBMs. RESULTS: The mechanisms that underlie the metastases of melanoma to the brain are unknown; therefore, it is necessary to identify pathways to target MBMs. Most patients with MBMs have short survival times. Recent use of immune-based and targeted therapies has changed the natural history of metastatic melanoma and may be effective for the treatment of patients with MBMs. CONCLUSIONS: Developing a better understanding of the factors responsible for MBMs will lead to improved management of this disease. In addition, determining the optimal treatments for MBMs and how they can be optimized or combined with other therapies, along with appropriate patient selection, are challenges for the management of this disease.

Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients.

PURPOSE: The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients. METHODS: A systematic review of the available literature was conducted. The body of evidence for the use of each agent, in each setting, was assigned a level of evidence. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible. RESULTS: A recommendation was developed in favor of patient-controlled analgesia with morphine in hematopoietic stem cell transplant (HSCT) patients. Suggestions were developed in favor of transdermal fentanyl in standard dose chemotherapy and HSCT patients and morphine mouth rinse and doxepin rinse in head and neck radiation therapy (H&N RT) patients. Recommendations were developed against the use of topical antimicrobial agents for the prevention of mucositis. These included recommendations against the use of iseganan for mucositis prevention in HSCT and H&N RT and against the use of antimicrobial lozenges (polymyxin-tobramycin-amphotericin B lozenges/paste and bacitracin-clotrimazole-gentamicin lozenges) for mucositis prevention in H&N RT. Recommendations were developed against the use of the mucosal coating agent sucralfate for the prevention or treatment of chemotherapy-induced or radiation-induced OM. No guidelines were possible for any other agent due to insufficient and/or conflicting evidence. CONCLUSION: Additional well-designed research is needed on prevention and management approaches for OM.

Impact of a New Portable Air Purification Technology Device in the Pediatric Hospital Setting - A Pre-post Assessment Study.

Introduction We assessed whether portable photo-electrochemical oxidation (PECO) air purification in the pediatric hospital room setting could improve health outcomes for patients admitted with respiratory distress.  Methods We performed a prospective study evaluating the use of a portable air purifier with PECO technology. The historical control group comprised matched patients. Twenty-seven PECO-equipped portable air filtration devices were placed in the rooms. Clinical endpoints included length of stay in the hospital, length of stay in the intensive care unit (ICU), rates of intubation, non-invasive ventilation, and nebulizer use. Results The mean length of ICU stay was 0.7 days in the pre-intervention period and decreased to 0.4 days post-intervention. The mean length of overall hospitalization reduced by 0.3 days. The rate of non-invasive ventilation use was 77% in the pre-intervention period and decreased to 23% in the post-intervention period. The rate of nebulizer use was 59% in the pre-intervention period and 41% in the post-intervention period. The rate of intubation was 57.1% in the pre-intervention period and 43% in the post-intervention period.  Conclusion  Portable PECO air purification may reduce hospital length of stay, rates of intubation, and need for non-invasive intervention and nebulizers for pediatric patients admitted with respiratory distress.

Effect of a Novel Photoelectrochemical Oxidation Air Purifier on Nasal and Ocular Allergy Symptoms.

BACKGROUND: Photoelectrochemical oxidation (PECO) is a new air purification technology developed to reduce circulating indoor allergens. PECO removes particles as small as 0.1 nm with the destruction of organic matter otherwise not trapped by a traditional filter and removes volatile organic compounds. OBJECTIVE: We hypothesized that with daily use, the device would reduce user nasal and ocular allergy total symptom scores (TSS) within 4 weeks. METHODS: The study was performed among 46 individuals with self-reported allergies using a portable PECO air purifier. Self-reported TSS were calculated at baseline and weekly for 4 weeks following initiation of continuous use of the system. TSS was the sum of total nasal symptom scores (TNSS) and total ocular symptom scores (TOSS) for the week. RESULTS: There was a statistically significant change in overall TSS from baseline to 4 weeks (10.1 at baseline and 4.35 postintervention) resulting in a mean difference of 5.75 (95% confidence interval [CI] 4.32-7.18; P < .0001). There was a statistically significant change in TNSS from baseline to 4 weeks (6.3 at baseline and 3.04 postintervention) resulting in a mean difference of 3.26 (95% CI 2.33-3.19; P < .0001). There was a statistically significant change in TOSS from baseline to 4 weeks (3.82 at baseline and 1.3 postintervention) resulting in a mean difference of 2.52 (95% CI 1.74-3.3; P < .0001). CONCLUSION: With the use of PECO air purification technology, TSS, TNSS, and TOSS decreased significantly. These improvements were consistent over the 4-week course of device use.

Role of Gamma Knife® Radiosurgery for the Treatment of Brain Metastases from Gynecological Cancers.

OBJECTIVE: Gamma Knife® (GK) (Elekta Instruments, Stockholm, Sweden) radiosurgery is well established for treatment of brain metastases. There are limited data on patients treated with GK from gynecological cancers. The authors sought to determine the effectiveness of the GK in patients with brain metastases from gynecological cancers. METHODS: An IRB-approved database was queried for patients with gynecologic cancers treated with GK between June 1996 and May 2016. Imaging studies were reviewed post-SRS (stereotactic radiosurgery) to evaluate local control (LC) and distant brain control (DC). Overall survival (OS), local control, and distant brain control were calculated using the Kaplan-Meier (KM) method and log-rank test.  Results: Thirty-three patients underwent SRS for 73 separate cranial lesions. The median age was -58.5 years, and 17 (52%) also had extracranial metastases. Ten (30%) patients had previously received whole brain radiotherapy (WBRT), and 11 (33%) underwent concurrent WBRT. The median tumor volume was 0.96 cm3. Median radiographic follow-up was 11 months. At the time of treatment, 39% of patients were categorized as recursive partitioning analysis (RPA) Class I, 55% as RPA Class II, and 6% as RPA Class III. The local failure rate was 8%. Five patients (15%) developed new brain lesions outside the radiation field with a median progression-free survival (PFS) of seven (range: 3-9) months. Median OS was 15 months from GK treatment. One-year OS was 72.9% from GK treatment. Primary cancer histology was a significant predictor of OS, favoring ovarian and endometrial cancer (p = 0.03). CONCLUSIONS: Gamma Knife stereotactic radiosurgery for gynecologic brain metastases leads to excellent control rates of treated lesions. Primary histology may have a significant impact on OS following GK, with improved survival seen with ovarian and cervical cancer following Gamma Knife radiosurgery (p = 0.03).

Outcomes Following Hypofractionated Stereotactic Radiotherapy in the Management of Brain Metastases.

OBJECTIVE: To evaluate the outcomes of patients treated with hypofractionated stereotactic radiotherapy (HSRT) for radiosensitive and radioresistant brain metastases. METHODS: Between August 2006 and July 2013, a total of 56 lesions in 44 patients with brain metastases were treated with HSRT. Twenty-three (41.1%) lesions were radioresistant. Patients were treated to a total dose of 24 to 30 Gy in 3 to 5 fractions. Median planning target volume was 6.18 cm. The primary endpoint for this study was local control with secondary endpoints of overall survival, distant failure, performance status, and treatment toxicity. RESULTS: The median follow-up for all patients was 5 months (range, 0.4 to 58.3 mo). Six- and 12-month Kaplan-Meier estimates of local control for all lesions were 85.6% and 79.4%, respectively. Radioresistant tumors had a 6- and 12-month local control rate of 87.0%, whereas radiosensitive tumors had a 6- and 12-month local control rate of 82.5% and 72.2%, respectively (P=0.41). Six- and 12-month distant brain control rates were 56.8% and 46.9%, respectively. Overall survival was significantly associated with recursive partitioning analysis classes I, II, and III (P=0.0003) and graded prognostic assessment classes 2 to 3 and 1 to 1.5 (P=0.041). CONCLUSIONS: HSRT is a safe and feasible alternative to single-session stereotactic radiosurgery for brain metastases. No difference was observed in local control rates between radioresistant and radiosensitive tumors.

Outcomes of mucosal melanoma of the head and neck.

INTRODUCTION: Mucosal melanoma of the head and neck is a rare disease with limited data available on outcomes; therefore, we reviewed our institutional experience. METHODS: An institutional database was queried and 38 patients with head and neck mucosal melanoma were identified. Charts were abstracted and local control (LC), progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: Most patients had T4 disease (86%), although nodes were positive in 11%. En bloc or endoscopic resection was performed on 93%. Adjuvant or definitive radiotherapy to a median dose of 60 Gy was utilized in 90%. Chemotherapy was given in 21%, and 16% received interferon. Three-year LC, PFS and OS were 90%, 48% and 59%, respectively. Median OS was 4.6 years. Site of first failure was distant in 52% of cases. CONCLUSION: With aggressive therapy median OS was 4.6 years in this cohort. Distant recurrence remains the primary mode of failure. It may be reasonable to include mucosal melanoma patients in trials of systemic agents along with high-risk cutaneous melanomas.

Comparison of every 3 week cisplatin or weekly cetuximab with concurrent radiotherapy for locally advanced head and neck cancer.

BACKGROUND: Cisplatin dosed every 3 weeks (CIS) or weekly cetuximab (CTX) concurrent with radiotherapy are standards of care for locally advanced head and neck squamous cell carcinoma (LAHNC). Retrospective comparisons of CIS and CTX have offered mixed conclusions. We compared outcomes between CIS and CTX in this patient population. METHODS: Between January 2006 and December 2011, we identified 279 patients who underwent definitive radiotherapy and concurrent systemic therapy for LAHNC. The median age difference between the CIS and CTX groups was relatively small (58 vs. 62 years, respectively) and CIS patients had a slightly higher rate of N2 disease than CTX patients (74% vs. 61%, respectively). RESULTS: Median follow-up was 27 months. Systemic therapy consisted of CIS in 241 (86.4%) and CTX in 38 (13.6%). Actuarial locoregional control of the CIS and CTX groups at 2 years were 91% and 90% (p=0.74), respectively. Actuarial 2 year distant metastasis rates between the groups were 8% and 12%, respectively (p=0.55), and actuarial 2 year overall survival between the groups were 87% and 89%, respectively (p=0.47). CONCLUSIONS: We found no difference in locoregional control, distant metastasis rate, or overall survival between patients treated with concurrent CIS or CTX.

Postoperative concurrent chemotherapy and radiotherapy for high-risk cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Despite resection followed by adjuvant radiotherapy, high-risk cutaneous squamous cell carcinomas of the head and neck region (SCCHN) often recur. Because adjuvant concurrent chemoradiation reduces recurrence among high-risk mucosal SCCHN, we sought to understand its efficacy among high-risk cutaneous SCCHN. METHODS: We conducted a retrospective cohort study of patients with cutaneous SCCHN who underwent adjuvant radiation or concurrent chemoradiation. Patients must have had stage III/IV with high-risk features, including metastatic involvement of ≥2 lymph nodes, positive margins, or extracapsular invasion. RESULTS: There were 61 patients: 27 (44%) received adjuvant radiation and 34 (56%) received adjuvant chemoradiation. The median recurrence-free survivals were 15.4 and 40.3 months, respectively. Adjuvant chemoradiation significantly decreased the risk of recurrence or death in a multivariable analysis: hazard ratio (HR) 0.31 (p = .01). However, a difference in overall survival was not found. CONCLUSION: For high-risk cutaneous SCCHN, adjuvant chemoradiation was associated with a better recurrence-free survival than adjuvant radiation alone.

Potential role for LINAC-based stereotactic radiosurgery for the treatment of 5 or more radioresistant melanoma brain metastases.

OBJECT: Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) is a treatment option for patients with melanoma in whom brain metastases have developed. Very limited data are available on treating patients with ≥5 lesions. The authors sought to determine the effectiveness of SRS in patients with ≥5 melanoma brain metastases. METHODS: A retrospective analysis of metastatic melanoma treated with SRS in a single treatment session for ≥5 lesions was performed. Magnetic resonance imaging studies were reviewed post-SRS to evaluate local control (LC). Disease progression on imaging was defined using the 2009 Response Evaluation Criteria in Solid Tumors (RECIST). Survival curves were calculated from the date of brain metastases diagnosis or the date of SRS by using the Kaplan-Meier (KM) method. Univariate and multivariate analysis (UVA and MVA, respectively) were performed using the Cox proportional-hazards model. RESULTS: The authors identified 149 metastatic brain lesions treated in 28 patients. The median patient age was 60.5 years (range 38-83 years), and the majority of patients (24 [85.7%]) had extracranial metastases. Four patients (14.3%) had received previous whole-brain radiotherapy (WBRT), and 11 (39.3%) had undergone previous SRS. The median planning target volume (PTV) was 0.34 cm3 (range 0.01-12.5 cm3). Median follow-up was 6.3 months (range 1-46 months). At the time of treatment, 7% of patients were categorized as recursive partitioning analysis (RPA) Class I, 89% as RPA Class II, and 4% as RPA Class III. The rate of local failure was 11.4%. Kaplan-Meier LC estimates at 6 and 12 months were 91.3% and 82.2%, respectively. A PTV volume≥0.34 cm3 was a significant predictor of local failure on UVA (HR 16.1, 95% CI 3.2-292.6, p<0.0001) and MVA (HR 14.8, 95% CI 3.0-268.5, p=0.0002). Sixteen patients (57.1%) were noted to have distant failure in the brain with a median time to failure of 3 months (range 1-15 months). Nine patients with distant failures received WBRT, and 7 received additional SRS. Median overall survival (OS) was 9.4 and 7.6 months from the date of brain metastases diagnosis and the date of SRS, respectively. The KM OS estimates at 6 and 12 months were 57.8% and 28.2%, respectively, from the time of SRS treatment. The RPA class was a significant predictor of KM OS estimates from the date of treatment (p=0.02). Patients who did not receive WBRT after SRS treatment had decreased OS on MVA (HR 3.5, 95% CI 1.1-12.0, p=0.03), and patients who did not receive WBRT prior to SRS had improved OS (HR 0.11, 95% CI 0.02-0.53, p=0.007). CONCLUSIONS: Stereotactic radiosurgery for ≥5 lesions appears to be effective for selected patients with metastatic melanoma, offering excellent LC. This is particularly important for patients as new targeted systemic agents are improving outcomes but still have limited efficacy within the central nervous system.

Clinicopathologic predictors of survival in patients with desmoplastic melanoma.

BACKGROUND AND OBJECTIVES: Desmoplastic melanoma is a unique subtype of melanoma which typically affects older patients who often have comorbidities that can adversely affect survival. We sought to identify melanoma-specific factors influencing survival in patients with desmoplastic melanoma. METHODS: Retrospective review from 1993 to 2011 identified 316 patients with primary desmoplastic melanoma. Clinicopathologic characteristics were correlated with nodal status and outcome. RESULTS: Fifty-five patients (17.4%) had nodal disease: 33 had a positive sentinel lymph node biopsy and 22 developed nodal recurrences (no sentinel lymph node biopsy or false-negative sentinel lymph node biopsy). Nodal disease occurred more often in younger patients and in cases with mixed compared with pure histology (26.7% vs. 14.6%); both of these variables significantly predicted nodal status on multivariable analysis (p<0.05). After a median follow-up of 5.3 years, recurrence developed in 87 patients (27.5%), and 111 deaths occurred. The cause of death was known in 79 cases, with 47 deaths (59.5%) being melanoma-related. On multivariable analysis, Breslow thickness, mitotic rate ≥ 1/mm(2) and nodal status significantly predicted melanoma-specific survival (p<0.05). CONCLUSIONS: Nodal status predicts melanoma-specific survival in patients with desmoplastic melanoma. However, since patients with desmoplastic melanoma represent an older population, and a considerable proportion of deaths are not melanoma-related (40.5%), comorbidities should be carefully considered in making staging and treatment decisions in this population.

Annular erythema responding to tacrolimus ointment.

Annular erythema is an unusual, often idiopathic disorder that tends to respond poorly to topical therapy. Two patients with idiopathic, topical corticosteroid-resistant annular erythema showed prompt clearing of lesions treated with 0.1% tacrolimus ointment and persistence of untreated ones which themselves responded to subsequent treatment. These two cases demonstrate a clear-cut therapeutic response of chronic, topical corticosteroid-resistant annular erythema to topical tacrolimus ointment 0.1% BID. Additional experience with tacrolimus ointment, hopefully in controlled circumstances, should clarify its potential value in treating annular erythema.

Altered fractionation schedules in radiation treatment: a review.

Conventionally fractionated radiotherapy is delivered in 1.8- to 2.0-Gy fractions. With increases in understanding of radiation and tumor biology, various alterations of radiotherapy schedules have been tested in clinical trials and are now regarded by some as standard treatment options. Hyperfractionation is delivered through a greater number of smaller treatment doses. Accelerated fractionation decreases the amount of time over which radiotherapy is delivered typically by increasing the number of treatments per day. Hypofractionation decreases the number of fractions delivered by increasing daily treatment doses. Furthermore, many of these schedules have been tested with concurrent chemotherapy regimens. In this review, we summarize the major clinical studies that have been conducted on altered fractionation in various disease sites.

Phase II multicenter trial of Caphosol for the reduction of mucositis in patients receiving radiation therapy for head and neck cancer.

PURPOSE: We conducted a phase II multicenter study evaluating Caphosol in patients receiving head and neck radiation (H/N RT) +/- chemotherapy or biologic sensitizer. MATERIALS/METHODS: The primary endpoint of the study tested the rate of functional mucositis (WHO grade > or equal to 2) with the hypothesis that <75% of patients would develop > or equal to 2 mucositis with Caphosol compared with a historical rate of >90%. New methods were applied with higher than historic rigor. 5 Institutions were included in this study: Moffitt Cancer Center (MCC), MD Anderson Cancer Center (MDACC), Duke University Cancer Center (DUCC), University of Florida (UF) and Temple University Cancer Center (TUCC). Caphosol was taken by patients at least 4 times a day and up to 10 times per day commencing with day 1 of RT and for a total duration of 8 weeks after completion of RT. Detailed questionnaires were completed weekly by patients and a unique algorithm was used to generate the WHO grade of mucositis. RESULTS: 98 Patients were enrolled in the study. 59/98 (60%) patients were evaluable for the primary endpoint giving us 80% power. All evaluable patients experienced WHO grade > or equal to 2 mucositis and the trial failed to reject the null hypothesis. > or equal to 2 mucositis rates at weeks 2, 4, 6, 11 and 15 were as follows: 45%, 90%, 98%, 71%, 50%. CONCLUSION: We were unable to demonstrate that Caphosol significantly reduced WHO grade 2 or higher mucositis below a 90% historic rate. We are not surprised with this finding given our rigorous methodology in grading.