M.A. Neben-Wittich

Radiotherapy for Extramedullary Plasmacytoma of the Head and Neck

PURPOSE To define the effectiveness of radiotherapy in the treatment of patients with extramedullary plasmacytoma of the head and neck (EMPHN). METHODS AND MATERIALS We searched the Mayo Clinic Rochester Department of Radiation Oncology electronic Tumor Registry and identified 18 consecutive patients with a diagnosis of solitary EMPHN. Sixteen patients were treated with radiotherapy at initial diagnosis and 2 received salvage radiotherapy for local failure after surgery. Median dose administered was 50.4 Gy. Median follow-up was 6.8 years. RESULTS One patient (6%) developed a marginal recurrence 12 months after treatment. Six patients (33%) developed multiple myeloma (2 patients) or plasmacytomas at distant sites (4 patients) at a median of 3.1 years after diagnosis (range, 0.02 to 9.6 years). Median and 5- and 10-year overall survival rates from the date of diagnosis are 12.5 years, 88%, and 55%, respectively. Two patients (11%) developed a radiation-induced malignancy at 6.5 and 6.9 years after treatment. CONCLUSIONS Radiotherapy provides excellent local and regional tumor control and survival in patients with EMPHN. To the best of our knowledge, this is the first report of presumed radiation-induced malignancy in this patient population.

Adjuvant chemoradiation therapy with high-dose versus weekly cisplatin for resected, locally-advanced HPV/p16-positive and negative head and neck squamous cell carcinoma.

OBJECTIVES Standard treatment for patients with poor-risk, resected head and neck squamous cell carcinoma (HNSCC) is adjuvant radiation therapy combined with high-dose cisplatin. Many patients are treated with weekly cisplatin; it is not known whether weekly and high-dose cisplatin are equivalent. This study compares the outcomes of patients with locally-advanced HPV-negative HNSCC and HPV/p16-positive oropharynx HNSCC treated with adjuvant chemoradiation therapy with either high-dose or weekly cisplatin. MATERIALS AND METHODS Retrospective review of patients with Stage III/IV HNSCC who had surgery followed by adjuvant chemoradiation therapy at Mayo Clinic, Rochester. HPV and/or p16 status was available for all oropharynx patients. RESULTS 104 Patients (51 high-dose, 53 weekly) were analyzed. The 3-year overall survival was 84% and 75% for patients who received high dose and weekly cisplatin, respectively (p=0.30). The 3-year recurrence free survival was 71% and 74% in the high dose and weekly cisplatin group, respectively (p=0.95). Patients with HPV/p16-positive oropharynx cancer who received adjuvant chemoradiation therapy with high-dose and weekly cisplatin had three-year overall survival rates of 91% and 86% (p=0.56), and 3-year recurrence free survival of 84% and 82% (p=0.93). Extracapsular extension did not affect prognosis in either group. CONCLUSIONS No significant survival difference was seen between patients with locally advanced HNSCC treated with adjuvant chemoradiation therapy with high-dose or weekly cisplatin, although there was a trend for improved survival with high-dose cisplatin. Weekly cisplatin in the adjuvant setting may be a better treatment for patients with HPV-positive oropharynx cancer to preserve survival and minimize toxicity.

Comparison of Provider-Assessed and Patient-Reported Outcome Measures of Acute Skin Toxicity During a Phase III Trial of Mometasone Cream Versus Placebo During Breast Radiotherapy: The North Central Cancer Treatment Group (N06C4)

PURPOSE Considerable interobserver variability exists among providers and between providers and patients when measuring subjective symptoms. In the recently published Phase III N06C4 trial of mometasone cream vs. placebo to prevent radiation dermatitis, the primary provider-assessed (PA) endpoint, using the Common Toxicity Criteria for Adverse Events (CTCAE), was negative. However, prospectively planned secondary analyses of patient-reported outcomes (PROs), using the Skindex-16 and Skin Toxicity Assessment Tool (STAT), were positive. This study assesses the relationship between PA outcomes and PROs. METHODS AND MATERIALS Pearson correlation coefficients were calculated to compare the three tools. Statistical correlations were defined as follows: <0.5, mild; 0.5-0.7, moderate; and >0.7, strong. RESULTS CTCAE dermatitis moderately correlated with STAT erythema, and CTCAE pruritus strongly correlated with STAT itching. CTCAE pruritus had a moderate correlation with Skindex-16 itching. Comparing the 2 PRO tools, Skindex-16 itching correlated moderately with STAT itching. Skindex-16 burning, hurting, irritation, and persistence all showed the strongest correlation with STAT burning; they showed moderate correlations with STAT itching and tenderness. CONCLUSIONS The PRO Skindex-16 correlated well with the PRO portions of STAT, but neither tool correlated well with CTCAE. PROs delineated a wider spectrum of toxicity than PA measures and provided more information on rash, redness, pruritus, and annoyance measures compared with CTCAE findings of rash and pruritus. PROs may provide a more complete measure of patient experience than single-symptom, PA endpoints in clinical trials assessing radiation skin toxicity.

Successful treatment of severe extremity pain in myelofibrosis with low-dose single-fraction radiation therapy.

Myelofibrosis (MF) is characterized by cytopenias/cytoses, leukoerythroblastic blood picture, bone marrow fibrosis, and extramedullary hematopoiesis. Extremity bone pain can be a feature of MF. There has been one case report of a patient with MF and bone pain treated with radiation. We treated five patients with MF and extremity pain with radiation at our institution between 2004 and 2010. All patients had severe pain unresponsive to narcotic medication. Radiation was one fraction of 100 to 600 cGy. Most patients saw improvement in the pain within days and achieved a complete response within days to weeks.The response lasted between 1 month and 2 years. Retreatment was performed in four patients and achieved a durable response in three patients. No patients reported any acute or late side effects from radiation.Bone involvement in MF can cause disabling pain, but single-fraction low-dose radiation is a safe and effective treatment, often leading to a durable response. Retreatment is also safe and effective inpatients who experience recurrent pain.

Effective management of accelerated phase myelofibrosis with low-dose splenic radiotherapy†

The main cause of hepatosplenomegaly in primary (PMF), post polycythemia vera (post-PV MF), and post essential thrombocythemia (post-ET MF) myelofibrosis (MF) is extramedullary hematopoiesis (EMH). Drug-refractory symptomatic splenomegaly in MF is usually managed by splenectomy or involved-field radiotherapy. The latter is most effective in the treatment of MF-associated bone pain and pulmonary hypertension.Our previous experience with hepatosplenic radiotherapy in MF showed efficacy in the majority of treated patients but its utility was limited by the transient nature of its benefit and the occurrence of treatment-related pancytopenia. In an effort to address these issues,we have adopted an induction-maintenance treatment strategy that utilizes lower radiation doses-induction with 100 cGy total in four daily doses of 25 cGy and maintenance with either the same or lower intensity regimen. Herein, we report our most recent experience using this treatment plan in two cases, who in addition to their expected response from the standpoint of splenomegaly, also unexpectedly showed a marked response of their underlying accelerated phase disease,including clearance of circulating blasts and basophilia.

Late tumor pseudoprogression followed by complete remission after lung stereotactic ablative radiotherapy

Lung stereotactic ablative radiotherapy (SABR) has recently become more common in the management of patients with early-stage non-small cell lung cancer (NSCLC) and metastatic lung lesions who are not surgical candidates. By design, SABR is applied to small treatment volumes, using fewer but significantly higher dose fractions, and steep dose gradients. This treatment theoretically maximizes tumor cell death and decreases the risk of damage to the surrounding normal tissues. Local control rates for SABR in early stage lung cancer remain high. Since the numbers of primary tumor recurrences is small, some debate exists as to the appropriate definition of treatment failure. Controversies remain regarding the most appropriate interpretation of imaging tests obtained to evaluate treatment outcomes after lung SABR. Most definitions of progression include an increasing diameter of target lesion which can be problematic given the known mass-like consolidation seen on CT imaging after ablative therapy. Here, we present a case report illustrative of the pitfalls of relying solely on anatomic imaging to determine SABR treatment failure.

Medical factors influencing decision making regarding radiation therapy for breast cancer

Radiation therapy is an important and effective adjuvant therapy for breast cancer. Numerous health conditions may affect medical decisions regarding tolerance of breast radiation therapy. These factors must be considered during the decision-making process after breast-conserving surgery or mastectomy for breast cancer. Here, we review currently available evidence focusing on medical conditions that may affect the patient–provider decision-making process regarding the use of radiation therapy.

Adjuvant hypofractionated intensity modulated radiation therapy after resection of regional lymph node metastases in patients with cutaneous malignant melanoma of the head and neck

PURPOSE To evaluate outcomes in patients with malignant melanoma of the head and neck with resected regional lymph node (LN) metastases treated with adjuvant hypofractionated intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS A retrospective review was performed of 46 patients with malignant melanoma of the head and neck with regional LN metastases treated with lymphadenectomy and adjuvant IMRT. Patients underwent neck dissection (n = 42) or local excision (n = 4) for regional metastases at initial diagnosis (n = 19) or recurrence (n = 27). Adjuvant IMRT was delivered twice per week over 2.5 weeks for a total dose of 30 Gray (Gy) in 5 fractions. Acute and late adverse events were recorded using the Common Toxicity Criteria for Adverse Events version 4. Site of first recurrence was defined as local-regional (LR, above the clavicles) or distant. Overall survival, disease-free survival, and disease recurrence risks were determined using Kaplan-Meier estimates. RESULTS The median follow-up in living patients was 2.8 years (range, 0.2-6.9). Most patients experienced acute grade 1-2 dermatitis (80%) and mucositis (85%). One patient (2%) experienced an acute grade 3 adverse event. Seven patients (16%) experienced late grade 2 adverse events. No patient experienced grade 3 or higher late adverse events. Site of first recurrence was LR alone (n = 5), both LR and distant (n = 1), and distant alone (n = 25). Five of the 6 LR recurrences were inside the IMRT planning target volume (PTV). In-PTV and total LR control at 3 years were 85% and 76%, respectively. Overall survival and disease-free survival at 3 years were 63% and 25%, respectively. CONCLUSIONS Adjuvant hypofractionated IMRT (30 Gy in 5 fractions) was associated with a high rate of in-PTV control and a low risk of serious adverse events.

Adjuvant chemoradiotherapy for resected pancreas cancer

The purpose of this article is to review pertinent literature assessing the evidence regarding adjuvant chemoradiotherapy for adenocarcinoma of the pancreas following curative resection. This review looks at randomized controlled studies with the emphasis on adjuvant chemoradiotherapy. In assessing the evidence from the studies reviewed in this article, the trials have been grouped according to the positive or negative results for or against adjuvant treatment. In addition, data from two large, single-institution studies affirming the role for adjuvant chemoradiotherapy has been included. Understanding the evidence from all of the randomized studies is important in shaping current practice recommendations for adjuvant therapy of surgically resected pancreas cancer. Adjuvant chemoradiotherapy following surgery is the current approach at many cancer treatment centers in the United States. In Europe, chemotherapy alone is the preferred adjuvant therapy. However, the type of adjuvant treatment recommended remains controversial due to conflicting study results. The debate will likely continue. Current practice should be based on the weight of evidence available at this time, which is in favor of adjuvant chemotherapy with chemoradiotherapy.

Technique for the administration of high-dose-rate brachytherapy to the bile duct using a nasobiliary catheter

PURPOSE Cholangiocarcinoma patients who are potential candidates for liver transplantation may be treated with high-dose-rate (HDR) brachytherapy using a minimally invasive nasobiliary catheter in an effort to escalate the radiotherapy dose to the tumor and maximize local control rates. This work describes the equipment, procedures, and quality assurance (QA) that enables successful administration. METHODS AND MATERIALS This work describes the nasobiliary catheter placement, simulation, treatment planning, treatment delivery, and QA. In addition, a chart review was performed of all patients who received endoscopic retrograde cholangiopancreatography for HDR bile duct brachytherapy at our institution from 2007 to 2017. The review evaluated how many patients were treated and the number of patients who could not be treated because of anatomic and/or equipment limitations. RESULTS From 2007 to 2017, 122 cholangiocarcinoma patients have been treated with HDR brachytherapy using a nasobiliary catheter. Three patients underwent catheter placement but did not receive brachytherapy treatment due to catheter migration between placement and treatment or because the HDR afterloader was unable to extend the source wire into the treatment site. Periodic QA is recommended for ensuring whether the HDR afterloader is capable of extending the source wire through an extensive and curved path. CONCLUSIONS Intraluminal HDR brachytherapy with a nasobiliary catheter can be successfully administered. Procedures and QA are described for ensuring safety and overcoming technical challenges.