Proton Beam Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma.

Purpose: To discuss the role of proton beam therapy (PBT) in the treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC). Materials and Methods: A review of the pertinent literature. Results: Proton beam therapy likely results in reduced acute and late toxicity as compared with intensity-modulated radiation therapy (IMRT). The extent of the reduced toxicity, which may be modest, depends on the endpoint and technical factors such as pencil beam versus passive scattered PBT and adaptive replanning. The disease control rates after PBT are likely similar to those after IMRT. Conclusion: Proton beam therapy is an attractive option to treat patients with OPSCC. Whether it becomes widely available depends on access.

Carbon Ion Radiotherapy in the Management of Hepatocellular Carcinoma.

Localized hepatocellular carcinoma (HCC) that is unresectable and non-transplantable can be treated by several liver-directed therapies. External beam radiation therapy (EBRT) is an increasingly accepted and widely utilized treatment modality in this setting. Accelerated charged particles such as proton beam therapy (PBT) and carbon ion radiation therapy (CIRT) offer technological advancements over conventional photon radiotherapy. In this review, we summarize the distinct advantages of CIRT use for HCC treatment, focusing on physical and biological attributes, and outline dosimetric and treatment planning caveats. Based on these considerations, we posit that HCC may be among the best indications for use of CIRT, as it allows for maximizing tumoricidal doses to the target volume while minimizing the dose to the organs at risk.

Primary Mediastinal B Cell Lymphoma in the Positron-Emission Tomography Era Executive Summary of the American Radium Society Appropriate Use Criteria.

PURPOSE: Primary mediastinal B cell lymphoma (PMBCL) is a highly curable subtype of non-Hodgkin lymphoma that is diagnosed predominantly in adolescents and young adults. Consequently, long-term treatment-related morbidity is critical to consider when devising treatment strategies that include different chemoimmunotherapy strategies with or without radiation therapy. Furthermore, adaptive approaches using the end-of-chemotherapy (EOC) positron emission tomography (PET)/computed tomography (CT) scanning may help to determine which patients may benefit from additional therapies. We aimed to develop evidence-based guidelines for treating these patients. METHODS AND MATERIALS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the PubMed database. The ARS expert committee, composed of radiation oncologists, hematologists, and pediatric oncologists, developed consensus guidelines using the modified Delphi framework. RESULTS: Nine studies met the full criteria for inclusion based on reporting outcomes on patients with primary mediastinal B cell lymphoma with EOC PET/CT response scored with the 5-point Deauville scale. These studies formed the evidence for these guidelines in managing patients with PMBCL according to the EOC PET response, including after a 5-point Deauville scale of 1 to 3, 4, or 5, and for patients with relapsed and refractory disease. The expert group also developed guidance on radiation simulation, treatment planning, and plan evaluation based on expert opinion. CONCLUSIONS: Various treatment approaches exist in the management of PMBCL, including different chemoimmunotherapy regimens, the use of consolidative radiation therapy, and adaptive approaches based on EOC PET/CT response. These guidelines can be used by practitioners to provide appropriate treatment according to different disease scenarios.

Long-term Outcomes After Definitive Radiation Therapy for Solitary Plasmacytoma.

OBJECTIVE: Definitive radiotherapy (RT) with or without surgery is the standard of care for solitary plasmacytoma. Here, we report clinical outcomes for this rare malignant neoplasm. PATIENTS AND METHODS: We retrospectively reviewed the medical records of adults with solitary plasmacytoma treated with definitive RT between 1963 and 2015 at a single institution, and assessed disease control, survival, and toxicity per Common Terminology Criteria for Adverse Events (CTCAE), version 4. RESULTS: A total of 42 patients with solitary plasmacytoma of the bone (SPB, n=27) or extramedullary plasmacytoma (EMP, n=15) were treated with definitive RT with (n=11) or without (n=31) surgical resection. The median age at diagnosis was 59 years (range: 28 to 76 y).Twenty-two patients had tumors ≥5 cm and 20 had tumors <5 cm. Immunoglobulins were elevated in 23 patients and M-protein in 14. The median RT dose was 45 Gy (range: 15 to 54 Gy) over a median 25 fractions (range: 1 to 38 fractions) with 3 patients receiving twice-daily fractionation and 6 received elective nodal irradiation. No patients received adjuvant chemotherapy. The median follow-up was 10.3 years. The 10-year local control rate after RT was 88%. Five patients who developed a local recurrence had SPB ≥5 cm. The 10-year multiple myeloma-free survival rates were: overall, 47%; SPB, 24%; and EMP, 87% (P=0.0012). The 10-year cause-specific survival rate was 75%: 64% for SPB versus 93% for EMP (P=0.0116). The 10-year overall survival rate was 60%. Three patients experienced late grade 2+ toxicity. CONCLUSIONS: Definitive RT with moderate doses results in excellent local control. We observed a higher rate of progression to multiple myeloma and lower survival in patients with SPB compared with EMP.

Radiation treatment of soft palate squamous cell carcinoma.

BACKGROUND: To report our institution's experience treating soft palate squamous cell carcinoma with radiotherapy alone or combined with adjuvant chemotherapy and/or neck dissection for residual disease. METHODS: We analyzed 159 patients treated curatively between 1963 and 2016. Median follow-up was 4 years. RESULTS: The 5-year local control rates were T1, 90%; T2, 90%; T3, 70%; and T4, 59%. The 5-year cause-specific survival (CSS) rate was nearly identical for patients with stage I-III disease (88%, 86%, and 88%, respectively) compared to stage IVA/B (58%). Five-year overall survival was similar between patients with stage I-III disease (50%, 57%, and 54%, respectively) and approximately double that of patients with stage IVA/B disease (26%). Thirteen patients (8%) had severe complications related to radiotherapy. CONCLUSIONS: The likelihood of cure after definitive radiotherapy is relatively high in patients with stage I-III disease with soft palate carcinoma. Patients with stage IVA/B disease have a lower cure rate but with a 5-year CSS exceeding 50%.

Management of cutaneous Merkel cell carcinoma.

PURPOSE: To report the outcomes of patients with previously untreated cutaneous Merkel cell carcinoma (MCC) managed with curative intent. MATERIAL AND METHODS: Between December 1984 and August 2015, 59 patients with previously untreated cutaneous MCC were managed with curative intent with surgery and adjuvant radiotherapy (54 patients) or radiotherapy alone (5 patients) at the University of Florida. Primary sites included head and neck (45 patients), extremities (11 patients) and trunk (3 patients). Adjuvant chemotherapy was employed in 14 patients. Patients were staged according to the AJCC staging system: stage I, 25 patients; stage IIA, 7 patients; and, stage III, 27 patients. No patients had distant metastases. Median follow-up for all patients was 3.2 years (range, 0.3-20.9 years). Median follow-up for survivors was 6.7 years (range, 1.6-20.9 years). RESULTS: The 5-year outcomes were as follows: local control, 91%; regional control, 79%; local-regional control, 77%; disease metastasis-free survival, 60%; cause-specific survival, 53%; and overall survival, 39%. The 5-year outcomes for patients with stage I-IIA versus stage-III disease were the following: local-regional control, 90% versus 57% (p = .0115); distant metastasis-free survival, 78% versus 36% (p = .0002); cause-specific survival, 68% versus 35% (p = .0050); and overall survival, 48% versus 27% (p = .0377). Local-regional recurrences occurred in 12 patients; no patients were successfully salvaged. Severe late complications were observed in four patients. CONCLUSIONS: Although radiotherapy alone or combined with surgery results in a relatively high likelihood of local-regional control, the majority of recurrences are distant and approximately half of patients are cured. Patients with regional disease at diagnosis have significantly worse outcomes.

Radiotherapy alone or combined with chemotherapy for base of tongue squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: To evaluate the long-term disease control, survival, and complications after definitive radiotherapy (RT) alone or combined with adjuvant chemotherapy with or without planned neck dissection for base of tongue squamous cell carcinoma (SCC). STUDY DESIGN: We retrospectively reviewed the medical records of 467 patients treated at the University of Florida with definitive RT alone or combined with adjuvant chemotherapy between 1964 and 2011 for base of tongue SCC. METHODS: Median follow-up was 5.6 years. Median total dose to the primary site was 74.4 Gy. Eighty-seven patients (19%) were treated with once-daily fractionation, and 380 (81%) received altered fractionation schedules. Intensity-modulated RT was used in 128 patients (27%). Chemotherapy was administered to 173 (37%) patients. Planned neck dissection after RT was performed in 226 patients (48%). Data regarding p16 pathway activation were available for 25 patients. RESULTS: At 5 years, the local, local-regional, and regional control rates were 85.5%, 80.0%, and 90.0%, respectively. The 5-year overall, cause-specific, and distant metastasis-free survival rates were 59.1%, 71.5%, and 84.1%, respectively. Sixty-four patients (14%) developed one or more severe late complications. Fifty patients (11%) required late gastrostomy tube placement. CONCLUSIONS: This study supports the continued use of RT alone or combined with adjuvant chemotherapy for patients with base of tongue SCC, as this treatment yields high rates of cause-specific survival and disease control, with a relatively low rate of late complications. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1589-1594, 2017.

Long-term Outcome After Fractionated Radiotherapy for Pituitary Adenoma: The Curse of the Secretory Tumor.

OBJECTIVES: To determine the influence of secretory status on long-term outcome after fractionated radiotherapy (RT) for gross residual pituitary adenoma. MATERIALS AND METHODS: This is a retrospective study of 116 consecutively treated patients who met the following inclusion criteria: tissue diagnosis of pituitary adenoma, visible tumor at the time of RT, treatment with fractionated RT, and imaging follow-up of ≥2 years. Hypersecretion of growth hormone, adrenocorticotrophic hormone, prolactin, or thyroid-stimulating hormone was documented in 30 patients (26%). The RT dose in most (78%) patients was 45 Gy at 1.8 Gy per fraction. The major outcome endpoint is clinical and biochemical control, meaning no growth on follow-up scans and normalization of hypersecretion, if present before RT. RESULTS: Long-term tumor control was outstanding for nonsecretory tumors: 96% at 10 years. There was a major drop in the control rate of secretory tumors: 10-year clinical and biochemical control was 62% (P<0.0001 vs. 96%). Multivariate analysis confirmed secretory status as the only independent prognostic factor (variables analyzed were sex, age, tumor size, RT dose, and secretory status). CONCLUSIONS: Secretory pituitary adenomas have a worse prognosis than nonsecretory tumors after 45 to 50 Gy of conventionally fractionated RT. As a result of this finding, our plan is to increase the intensity of RT in secretory tumors, but our data did not evaluate this approach. The treatment guidelines that we currently use in pituitary adenoma are as follows. Radiosurgery (20 to 30 Gy) is our first-choice treatment of a secretory tumor that cannot be completely resected. When treating gross residual pituitary adenoma with fractionated RT, we use the following dose schedules: Nonsecretory: 45 Gy at 1.8 Gy/fraction, once-daily fractionation. Secretory: 54 Gy at 1.8 Gy/fraction once daily or 55.2 Gy at 1.2 Gy/fraction with twice-daily treatment.

Radiation therapy for nasal vestibule squamous cell carcinoma: a 40-year experience.

We evaluated the treatment of squamous cell carcinoma (SCC) of the nasal vestibule. Eighty-six patients were treated with radiotherapy (RT) and 13 patients received surgery and RT. The mean follow-up was: 9.7 years (range 4 months-35.9 years). The 5- and 10-year outcomes were: local control (LC), 88 and 82 %; local-regional control (LRC), 78 and 73 %; freedom from distant metastases (FFDM), 96 and 96 %; cause-specific survival (CSS), 91 and 86 %; and overall survival, 75 and 51 %. The 5- and 10-year LC rates for patients treated with RT were 94 and 89 % overall. A multivariate analysis was performed. Tumor size predicted LC, LRC, OS, and CSS. Overall stage predicted LRC. RT cures most patients with T1-T2 and favorable T4 SCCs with acceptable toxicity. RT and surgery result in improved likelihood of cure for patients with advanced T4 lesions.

Long-term Outcomes Following Radiotherapy for Adolescent Patients With Nonmetastatic WHO Type III Nasopharyngeal Carcinoma.

OBJECTIVES: To report long-term results of primary radiotherapy for nasopharyngeal cancer (NPC) presenting in the adolescent group. METHODS: Ten adolescent patients with World Health Organization (WHO) type III NPC were treated with primary radiotherapy at our institution between 1969 and 2007. Median age was 16.5 years (range, 11 to 21). Median radiotherapy dose to the primary target volume was 67.5 Gy (range, 60 to 74.8). The bilateral neck received 51.1 Gy (range, 50 to 60 Gy). Five patients were treated with once-daily radiotherapy and 5 received twice-daily radiotherapy. Three patients received neoadjuvant cisplatin and 5FU, and 1 patient received adjuvant maintenance cisplatin and 5FU. RESULTS: Median follow-up time was 9.5 years (range, 1.94 to 34.74). Fifteen-year overall survival, cause-specific survival, and progression-free survival rates were all 70%. Fifteen-year local and regional control rates were 100% and 90%. One patient recurred regionally and distantly simultaneously, and 2 patients developed distant metastases alone. All 3 died of their disease within 3 years. One patient died from multiple radiation-induced secondary meningiomas 34 years after radiotherapy. Five patients developed hypothyroidism, 3 developed sensorineural hearing loss, and 4 developed dental complications. The overall rates of CTCAE grade 3, 4, and 5 toxicity were 40%, 10%, and 10%, respectively. Despite high-radiation doses to the skull base, none of the patients in this study developed grade 3+ cognitive or vision toxicity. CONCLUSIONS: Radiotherapy achieves excellent local control in adolescent patients with unresectable WHO type III NPC. Our data support current protocols to systematically tailor treatment volumes and deescalate radiation doses to reduce treatment toxicity.

Impact of radiographic findings on for prognosis skin cancer with perineural invasion.

OBJECTIVES: Update our experience using radiotherapy (RT) for head-and-neck squamous or basal cell carcinoma with clinical perineural invasion (PNI) and correlate radiographic findings with outcomes. MATERIALS AND METHODS: We treated 65 patients with cT4N0 head-and-neck skin cancers with clinical PNI from 1965 to 2009 (N0 disease, 59; N1 disease, 6). Treatment included RT alone (N=18), RT with concurrent chemotherapy (N=14), surgery and postoperative RT (N=26), or postoperative RT with concurrent chemotherapy (N=5), and preoperative RT and surgery (N=2). Patients were stratified by imaging-negative disease (N=11), minimal or moderate peripheral disease (N=18), and macroscopic and/or central disease (N=36). Median RT dose was 72.6 Gy (50.4 to 79.2 Gy). Median follow-up overall and for living patients was 5.4 and 11.6 years, respectively. RESULTS: Five-year outcomes for imaging-negative disease versus minimal/moderate peripheral disease versus macroscopic/central disease were: local control, 81% versus 60% versus 47% (P=0.23); local-regional control, 80% versus 54% versus 47% (P=0.22); neck control, 100% versus 89% versus 93% (P=0.45); and distant metastasis-free survival, 89% versus 100% versus 93% (P=0.57), respectively. Five-year survival rates for imaging-negative disease versus minimal/moderate peripheral disease versus macroscopic/central disease were: overall survival, 82% versus 50% versus 52% (P=0.26), and cause-specific survival, 100% versus 58% versus 65% (P=0.08). Twenty-two (34%) patients had 1 or more severe (grade ≥3) late complications. CONCLUSIONS: There is a nonsignificant trend towards improved local control for imaging-negative patients and patients with minimal/moderate peripheral disease compared with macroscopic/central disease. Although survival appears better for imaging-negative patients, extent of imaging-positive PNI did not impact overall or cause-specific survival.

Esthesioneuroblastoma of the nasal cavity.

OBJECTIVES: Esthesioneuroblastoma is an uncommon cancer of the nasal cavity. We describe the outcomes for 26 patients treated with curative intent with photon radiotherapy (RT) at the University of Florida. METHODS: Between May 1972 and June 2007, 26 patients received RT for previously untreated esthesioneuroblastoma of the nasal cavity. Sixteen patients were males and 10 were females with a median age of 55 years (range, 3 to 82 y). The modified Kadish stage distribution was: B, 7 patients; C, 17 patients; and D, 2 patients. Treatment modalities included the following: definitive RT, 5 patients; preoperative RT, 2 patients; and postoperative RT after resection, 19 patients. Elective neck irradiation (ENI) was performed in 17 (71%) of 24 N0 patients. RESULTS: Rates of local control, cause-specific survival, and absolute overall survival at 5 years were 79%, 72%, and 69%, respectively. Overall survival among patients treated with definitive RT was 20% at 5 years, compared with 81% among those who underwent surgery and adjuvant RT (P=0.01). One (6%) of 17 patients who received ENI developed a recurrence in the neck and was successfully salvaged. Ultimate neck control was 100% at 5 years for patients who received ENI versus 69% among those not receiving ENI (P=0.0173). CONCLUSIONS: Resection combined with adjuvant RT is more effective than surgery or RT alone in the treatment of esthesioneuroblastoma. ENI reduces the risk of regional relapse in patients with Kadish stage B and C cancers.

Radiotherapy for dermatofibrosarcoma protuberans.

OBJECTIVES: Dermatofibrosarcoma protuberans (DFSP) is a rare indolent cutaneous tumor. In this analysis, we assess the effectiveness of postoperative radiotherapy (RT) in treating patients with DFSP. METHODS: From 1983 to 2011, 14 patients with DFSP were treated with RT at our institution. One patient had gross disease at the time of RT as he did not have a prior resection. The remaining 13 patients were treated with surgery and postoperative RT. Two patients had DFSP with a fibrosarcomatous component (DFSP-FS). External-beam RT was administered in a continuous course to doses ranging from 55.8 to 66.0 Gy. RESULTS: Follow-up ranged from 1.0 to 23.5 years (median, 10.5). Twelve patients (86%) with DFSP remained disease-free after RT; of those, 11 received postoperative RT and 1 received RT alone. One patient with DFSP-FS died with a local recurrence after surgery, external-beam RT, and a brachytherapy boost. Another patient with DFSP-FS died with diffuse metastatic disease to the lung and chest wall after surgery and RT. There were no serious complications from RT. CONCLUSIONS: RT may improve local control and reduce the risk of recurrence postoperatively in patients with DFSP.

Elective neck management for high-grade salivary gland carcinoma.

PURPOSE: To determine whether patients with clinically node negative (cNo) high grade salivary gland carcinomas benefit from an elective neck dissection prior to postoperative radiotherapy (RT). MATERIAL/METHODS: Between October 1964 and October 2009, 59 previously untreated patients with cNo high-grade salivary gland carcinomas (squamous cell carcinomas were excluded) were treated with curative intent using elective neck dissection (END; n=41), or elective neck irradiation (ENI; n=18) at the University of Florida College of Medicine (Gainesville, FL). All patients underwent resection of the primary cancer followed by postoperative RT. The median follow-up period was 5.2years (range, 0.3-34years). RESULTS: Occult metastases were found in 18 (44%) of the 41 patients in the END group. There were 4 recurrences (10%) in the END group and 0 recurrence in the ENI group. Neck control rates at 5years were: END, 90%; ENI, 100%; and overall, 93% (p=0.1879). Cause-specific survival was 94% in the ENI group, 84% in the END group, and 86% for all patients (p=0.6998). There were 3 reported grade 3 or 4 toxicities. Two patients had a postoperative fistula and one patient had a grade 4 osteoradionecrosis that required a partial mandibulectomy. CONCLUSIONS: Patients with cNo high grade salivary gland carcinomas who are planned to undergo surgery and postoperative RT likely do not benefit from a planned neck dissection.

Radiotherapy for pleomorphic adenoma.

PURPOSE: The aim of this study was to update our experience in treating pleomorphic adenoma with radiotherapy (RT). MATERIALS AND METHODS: This is a retrospective analysis of 25 patients treated with RT alone (2 patients) or combined with surgery (23 patients), with follow-up ranging from 1.8 to 34.9 years (median, 10.5 years). RESULTS: Local control was achieved in 13 (75%) of 16 patients with subclinical disease and 5 (56%) of 9 patients with gross disease. Overall local control was achieved in 18 (72%) of 25 patients. The 5-, 10-, and 15-year overall local control rates were 76 %, 76%, and 68%, respectively. Ten patients died of the following causes: recurrent disease, 2; malignant transformation, 2; and intercurrent disease, 6. At last follow-up, 14 patients were alive without evidence of disease, and 1 patient was alive with disease. Dental carries and transient facial nerve deficits were the most common complications. No patients developed severe complications subsequent to RT. CONCLUSIONS: In patients at high risk for developing recurrent pleomorphic adenoma after surgery, RT is effective in controlling subclinical disease.

Adenoid cystic carcinoma of the head and neck.

PURPOSE: To report our experience using radiotherapy alone or combined with surgery to treat adenoid cystic carcinoma of the head and neck. MATERIALS AND METHODS: Radiotherapy alone or combined with surgery was used to treat 120 previously untreated patients with adenoid cystic carcinoma (ACC) of the head and neck from August 1966 to March 2008. Patients were treated with curative intent. American Joint Committee on Cancer stage distribution was,T0 (n = 1), T1 (n = 26), T2 (n = 25), T3 (n = 14), T4 (n = 54), N0 (n = 113), N1 (n = 2), N2a (n = 1), N2b (n = 2), and N2c (n = 2). Treatment included surgery with postoperative radiotherapy (n = 71), radiotherapy alone (n = 46), and preoperative radiotherapy and surgery (n = 3). Incidental and clinical perineural invasion was found in 41 (34%) and 35 (29%) patients, respectively. Median follow-up was 8.6 and 11.6 years overall and among living patients, respectively. RESULTS: The 10-year overall, cause-specific, and distant metastasis-free survival rates, respectively, were as follows: radiotherapy alone, 37%, 46%, and 76%; surgery and radiotherapy, 57%, 71%, and 62%; and overall, 50%. The 10-year local control rates were as follows: radiotherapy alone, 36%; surgery and radiotherapy, 84%; and overall, 65%. The 10-year neck control rates were as follows: elective nodal irradiation (ENI), 98%; no ENI, 89%; and overall, 95%. CONCLUSIONS: Surgery and adjuvant radiotherapy offer the best chance for cure for patients with resectable adenoid cystic carcinomas of the head and neck. Some patients with advanced, incompletely resectable disease can be cured with radiotherapy alone. ENI should be considered for primary sites located in lymphatic-rich regions.

Outcomes of patients with non-Hodgkin's lymphoma treated with Bexxar with or without external-beam radiotherapy.

PURPOSE: To compare the efficacy and toxicity of external-beam radiotherapy (EBRT) to sites of bulky lymphadenopathy in patients with chemotherapy-refractory low-grade non-Hodgkin's lymphoma (NHL) immediately before receiving Bexxar (tositumomab and (131)I) vs. in patients receiving Bexxar alone for nonbulky disease. METHODS AND MATERIALS: Nineteen patients with chemotherapy-refractory NHL were treated with Bexxar at our institution (University of Florida, Gainesville, FL) from 2005 to 2008. Seventeen patients had Grade 1-2 follicular lymphoma. Ten patients received a median of 20 Gy in 10 fractions to the areas of clinical involvement, immediately followed by Bexxar (EBRT + Bexxar); 9 patients received Bexxar alone. The median tumor sizes before EBRT + Bexxar and Bexxar alone were 4.8 cm and 3.3 cm, respectively. All 5 patients with a tumor diameter >5 cm were treated with EBRT + Bexxar. A univariate analysis of prognostic factors for progression-free survival (PFS) was performed. RESULTS: The median follow-up was 2.3 years for all patients and 3.1 years for 12 patients alive at last follow-up. Of all patients, 79% had a partial or complete response; 4 of the 8 responders in the EBRT + Bexxar group achieved a durable response of over 2 years, including 3 of the 5 with tumors >5 cm. Three of 9 patients treated with Bexxar alone achieved a durable response over 2 years. Actuarial estimates of 3-year overall survival and PFS for EBRT + Bexxar and Bexxar alone were 69% and 38% and 62% and 33%, respectively. The median time to recurrence after EBRT + Bexxar and Bexxar alone was 9 months. Having fewer than 4 involved lymph-node regions was associated with superior PFS at 3 years (63% vs. 18%). There was no Grade 4 or 5 complications. CONCLUSIONS: Adding EBRT immediately before Bexxar produced PFS equivalent to that with Bexxar alone, despite bulkier disease. Hematologic toxicity was not worsened. EBRT combined with Bexxar adds a safe and effective therapeutic treatment for managing recurrent low-grade follicular NHL.

Cutaneous Merkel cell carcinoma.

PURPOSE: The aim of this study was to describe the treatment outcomes of patients with cutaneous Merkel cell carcinoma managed with curative intent. MATERIALS AND METHODS: Between December 1984 and November 2009, 40 patients with previously untreated Merkel cell carcinoma were managed with curative intent with radiotherapy alone (3 patients) or combined with surgery (37 patients). Adjuvant chemotherapy was administered to 11 patients. Primary sites were the following: head and neck, 32 patients; extremities, 6 patients; and trunk, 2 patients. Patients were staged according to the Yiengpruksawan staging system: stage I, local disease; stage II, regional disease; and stage III, distant metastases. Twenty-four patients had stage I disease, and 16 patients had stage II disease. Median follow-up on all patients was 3.0 years (range, 0.6-15.6 years). Median follow-up on survivors was 4.2 years (range, 2.2-14.2 years). RESULTS: The 5-year outcomes were local control, 92%; regional control, 78%; local-regional control, 79%; distant metastasis-free survival, 57%; cause-specific survival, 45%; and overall survival, 36%. The 5-year outcomes for those with stage I vs stage II disease were the following: local-regional control, 87% and 67% (P = .1607); distant metastasis-free survival, 71% and 37% (P = .0073); cause-specific survival, 58% and 27% (P = .0090); and overall survival, 48% and 18% (P = .0037). Local-regional recurrences were observed in 6 patients; one patient was successfully salvaged. Severe complications were observed in 3 patients. CONCLUSIONS: Radiotherapy alone or combined with surgery results in a high local-regional control rate. The main mode of recurrence is distant. Approximately one half of patients are cured.

Skin carcinoma of the head and neck with perineural invasion.

PURPOSE: The aim of the study was to update the experience treating cutaneous squamous cell and basal cell carcinomas of the head and neck with incidental or clinical perineural invasion (PNI) with radiotherapy (RT). MATERIALS AND METHODS: From 1965 to 2007, 216 patients received RT alone or with surgery and/or chemotherapy. RESULTS: The 5-year overall, cause-specific, and disease-free survivals for incidental and clinical PNIs were 55% vs 54%, 73% vs 64%, and 67% vs 51%. The 5-year local control, local-regional control, and freedom from distant metastases for incidental and clinical PNIs were 80% vs 54%, 70% vs 51%, and 90% vs 94%. On univariate and multivariate (P = .0038 and .0047) analyses, clinical PNI was a poor prognostic factor for local control. The rates of grade 3 or higher complication in the incidental and clinical PNI groups were 16% and 36%, respectively. CONCLUSIONS: Radiotherapy plays a critical role in the treatment of this disease. Clinical PNI should be adequately irradiated to include the involved nerves to the skull base.

The significance of a marginal excision after preoperative radiation therapy for soft tissue sarcoma of the extremity.

BACKGROUND: Marginal excision of soft tissue sarcoma (STS), defined as resection through the tumor pseudocapsule or surrounding reactive tissue, increases the likelihood of local recurrence and necessitates re-excision or postoperative radiation. However, its impact after preoperative radiation therapy (RT) remains unclear. This study therefore investigated the significance of marginal margins in patients treated with preoperative RT for extremity STS, reporting long-term local control and limb preservation endpoints. METHODS: The records of 317 adults at the University of Florida with nonmetastatic extremity STS treated from 1980 to 2008 with preoperative RT as part of a limb conservation strategy were reviewed. The median follow-up was 4.7 years (8.3 years for living patients). The median tumor size was 10 cm (range, 2-36 cm), and 86% were high grade. The median RT dose was 50.4 Gy (range, 12.5-57.6 Gy). Margins were classified as wide/radical (n = 105), marginal (n = 179), contaminated (n = 15), positive (n = 17), or unknown (n = 1). Endpoints were local control (LC), amputation-free survival (AFS), cause-specific survival (CSS), and overall survival (OS). RESULTS: Five-year CSS and OS rates were 62% and 59%, respectively. Five-year LC and AFS was 93% and 89%, respectively. AFS by margin status was 64%, 83%, 97%, and 92% for positive, contaminated, marginal, and wide/radical margins, respectively (P<.005). Marginal excision following preoperative RT resulted in equivalent LC and AFS compared with wide/radical margins. CONCLUSIONS: Marginal resection after preoperative RT does not compromise LC or AFS in extremity STS. This finding may be related to radiosterilization of tumor cells within the reactive zone following preoperative RT.