Case Of Pneumonitis Research Articles

Preliminary Results Of a Phase II Study Of Single Agent Bay 80-6946, a Novel PI3K Inhibitor, In Patients With Relapsed/Refractory, Indolent Or Aggressive Lymphoma

IntroductionBAY 80–6946 is a potent and reversible Class I phosphatidylinositol-3-kinase (PI3K) inhibitor with significant activity against both PI3K-δ and PI3K-α isoforms. The PI3K-α inhibitory activity may overcome a PI3K-mediated mechanism of resistance triggered by PI3K-δ inhibition. A phase I dose-escalation study (Patnaik et al, ASH 2012) established the maximum tolerated dose of BAY 80-6946 (0.8 mg/kg) and reported promising activity (6/6 PR) in follicular lymphoma. In the present study we further investigated the activity and safety of BAY 80-6946 in patients with indolent or aggressive lymphoma subtypes that have progressed after standard therapy. MethodsPatients with histologically confirmed indolent or aggressive lymphoma relapsed or refractory to ≥2 prior lines of treatment were eligible. Patients received BAY 80-6946 at a dose of 0.8 mg/kg as a 1 hour infusion on days 1, 8 and 15 of a 28-day cycle. Patients continued on therapy until disease progression or unacceptable toxicity. Responses were assessed every two cycles according to the response criteria for lymphoma (Cheson et al., JCO 17:1244,1999) or the guidelines for diagnosis and treatment of chronic lymphocytic leukemia (CLL; Hallek et al., Blood111:5446-56, 2008). ResultsAs of July 31, 2013, a total of 61 lymphoma patients (27 indolent and 34 aggressive) were enrolled and 56 started study treatment. Patients were similarly distributed among indolent and aggressive cohorts with respect to gender (52% female), median age (68 yr, range 22-90) and ethnicity (76% Caucasian) and were heavily pretreated (median number of prior therapies: 3; prior Rituximab: 84%; prior ASCT: 20%). Other characteristics included advanced stage III-IV in 85% and B symptoms in 17%. The following entities were represented: follicular (FL; n=13); CLL (n= 11); marginal zone (MZL; n=3; none staged to date); diffuse large B-cell (DLBCL; n=18); mantle cell (MCL; n=7); transformed (n=5); and peripheral T-cell (PTCL; n=4). At the time of analysis patients had received between 1 and 5 cycles of treatment. Objective responses were seen across histologic subtypes (Table 1). At the time of this interim analysis, the overall response rate (RR) and complete RR were 40% and 20% in FL, 67% and 0% in CLL, 83% and 17% in MCL, and 50% and 0% in PTCL, respectively.Table 1Best response by lymphoma subtype in staged patientsFL (n=10)CLL (n=9)DLBCL(n=17)MCL(n=6)Transformed(n=5)PTCL(n=4)CR/CRu201100PR261412SD627020PD018122CR – complete response; CRu – CR unconfirmed; PR – partial response; SD – stable disease; PD – progressive diseaseGrade 3 adverse events (AE) were reported in 49% of patients, and grade 4 AE (all neutropenia) occurred in 15% of patients. Grade 3/4 AEs occurring in ≥5% of patients included hypertension (31%), neutropenia (16%), hyperglycemia (13%), diarrhea (5%) and fatigue (5%). Hyperglycemia of any grade occurred in 47%. Four patients required insulin therapy, but no grade 4 hyperglycemia was observed. Hypertension of any grade occurred in 46% of patients. Eight patients required antihypertensive treatment, but no grade 4 hypertension was reported. Diarrhea of any grade occurred in 25% of cases. No case of colitis was reported. There were two cases of interstitial pneumonitis, with both cases resolved following corticosteroid administration. Withdrawal of study drug due to AEs occurred in 10 patients (16%), and 4 patients required a dose reduction. Four deaths occurred; 1 due to progressive disease, 1 due to acute respiratory insufficiency, 1 due to Cryptococcal meningitis and 1 due to sepsis after start of a salvage chemotherapy regimen. ConclusionsThe novel PI3K inhibitor BAY 80-6946 is clinically active as a single agent and appears to have an acceptable toxicity profile in relapsed/refractory lymphoma. Preliminary efficacy results are encouraging, as promising activity has been observed in FL, CLL, MCL, and PTCL. The safety profile was consistent with prior studies. Further studies of this compound in patients with lymphoma are warranted. Disclosures:Vitolo:Roche: Speakers Bureau; Celgene: Speakers Bureau; Takeda: Speakers Bureau. Mappa:Bayer S.p.A.: Employment. Giurescu:Bayer Pharma AG: Employment. Childs:Bayer HealthCare Pharmaceuticals: Employment.

Pneumopathie induite par l’hydroxyurée

Hydroxyurea is an antimetabolite drug used in the treatment of myeloproliferative disorders. Common adverse effects include haematological, gastrointestinal cutaneous manifestations, and fever. Hydroxyurea-induced pneumonitis is unusual. A female patient was treated with hydroxyurea for polycythemia vera. She was admitted 20 days after commencing treatment with a high fever, productive cough, clear sputum and nausea. A chest CT-scan showed diffuse ground-glass opacities. Microbiological investigations were negative. The symptoms disappeared a few days after discontinuation of the drug and rechallenge led to a relapse of symptoms. Our case and 15 earlier cases of hydroxyurea-induced pneumonitis are reviewed. Two patterns of this disease may exist: an acute febrile form occurring within 1 month of introduction of hydroxyurea and a subacute form without fever. Even if uncommon, one should be aware of this complication of hydroxyurea.

A Case of Hypersensitivity Pneumonitis and Imaging Response to Treatment

SESSION TITLE: Interstitial Lung Disease Global Case Reports

AB1211 Newborns of mothers with autoimmune disease. Outcome in a regional hospital

BackgroundPregnant women with autoimmune disease (AID), particularly systemic lupus erythematosus (SLE), have increased risks of disease exacerbation, pre/eclampsia and other maternal and fetal complications. Low birth weight (LBW) for gestational...

Efficacy of exemestane and everolimus in HR positive (including HER2-neu positive) heavily pretreated cases of metastatic breast cancer in north India.

e11546 Background: M-Tor pathway is deregulated in significant percentage of patients with breast cancer. This pathway is responsible for tumor growth and metastasis especially in hormone receptor (HR) positive cases. Thus dual blockade of estrogen and M-Tor pathway has shown efficacy in this setting. Methods: Twenty patients with hormone receptor positive metatstatic breast cancer were treated with combination of everolimus 5 mg and exemestane 25 mg daily since November 2011. The median age was 53 years (age range- 32 to 75 years). All patients had two more sites of metastasis. 14 cases had 3 or more sites of metastasis. Liver- 10, lungs – 15, bones – 12, skin -3, lymph nodes – 10, and CNS – 5. Six of twenty cases were Her2 neu positive and were pretreated with Herceptin and lapatinib. All except 2 patients were treated with chemotherapy, 13 with minimum three lines of chemotherapy. All patients were ER and or PR positive and preteated with tamoxifen (5) and or aromatase inhibitors (anastrozole 9 and letrozole 11). The time gap between starting exemestane and everolimus and onset of metastatic disease was 2.5 years. Results: 7 out of 20 patients achieved disease control (either partial response-6 or stable disease -1). Out of 6 cases who were her2 neu positive, two achieved partial response. 5 out of 20 cases survive beyond nine months. Only two patients could go on to 10 mg daily everolimus. The dose limiting toxicity was development of oral ulcers. One patient had fever. No case of pneumonitis was noted with this dose. Conclusions: Combination of everolimus and exemestane is effective in HR positive cases and also in Her2 neu positive cases. 5 mg everolimus is well tolerated by most women. There is a need to further study the efficacy of this combinantion in Her2 neu positive cases.

Clinical efficacy and safety of lambrolizumab (MK-3475, Anti-PD-1 monoclonal antibody) in patients with advanced melanoma.

9009 Background: Programmed death-1 (PD-1) is an inhibitory T-cell co-receptor that may lead to suppression of antitumor immunity. Lambrolizumab is a humanized monoclonal IgG4 antibody against PD-1. This study explored the safety and clinical activity of lambrolizumab in patients (pts) with advanced melanoma (MEL). Methods: In this ongoing phase 1b expansion study of MEL pts with or without previous ipilimumab (IPI) treatment, lambrolizumab was administered IV every 2 or 3 weeks until disease progression or unacceptable toxicity. Tumor response was assessed every 12 weeks by independent, central, blinded radiographic review per immune-related response criteria and RECIST 1.1. Results: As of December 1, 2012, 294 pts with MEL were enrolled, including 179 IPI-naive and 115 IPI-pretreated. Pts received lambrolizumab 10 mg/kg (n = 183) or 2 mg/kg (n = 111). Preliminary data from the first 85 consecutive pts dosed before April 25, 2012, who had independent radiologic review available as of December 3, 2012, indicate a confirmed overall response rate per RECIST 1.1 of greater than 35%, pooled across all doses and schedules and including both IPI-naive and IPI-pretreated patients. The median duration of response has not been reached as only 2 pts who had initial response discontinued due to disease progression, but the duration of confirmed responses range from 28+ to 240+ days (up to 8+ months). Among 133 pts who were dosed with lambrolizumab before July 31, 2012, and evaluable for adverse events (AEs) as of September 28, 2012, fatigue (22%), rash (18%), and pruritus (14%) were the most common drug-related AEs (mostly grade 1/2). The incidence of drug-related grade 3/4 AEs was 10% (24% regardless of attribution). Four drug-related cases of pneumonitis were reported, all of grade 1/2. Grade 3/4 drug-related hypothyroidism (n = 1) and hyperthyroidism (n = 1) were noted. Conclusions: Preliminary data suggest that lambrolizumab has significant antitumor activity and is well tolerated with manageable side effects in both IPI-naive and IPI-pretreated MEL pts. These data have led to an ongoing, international, randomized study of lambrolizumab versus chemotherapy in IPI-pretreated MEL. Clinical trial information: NCT01295827.

TEP/TDM au FDG et toxicité pulmonaire à la bléomycine : à propos d’un cas clinique

Patients treated with bleomycin should be frequently monitored during and after treatment. Actually this treatment can cause pulmonary toxicity and may progress to pulmonary fibrosis. Extreme care is required in patients with a severe deterioration of renal function or impaired lung function. PET/CT can be a useful tool for the early diagnosis of this complication. We report a case of bleomycin-induced pneumonitis and discovered during a PET/CT performed for evaluation of Hodgkin's disease.

Proton Therapy for Breast Cancer After Mastectomy: Early Outcomes of a Prospective Clinical Trial

Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction. Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after the completion of therapy. All patients consented to have photographs taken for documentation of skin toxicity. Eleven of 12 patients had left-sided breast cancer. One patient was treated for right-sided breast cancer with bilateral implants. Five women had permanent implants at the time of RT, and 7 did not have immediate reconstruction. All patients completed proton RT to a dose of 50.4 Gy (relative biological effectiveness [RBE]) to the chest wall and 45 to 50.4 Gy (RBE) to the regional lymphatics. No photon or electron component was used. The maximum skin toxicity during radiation was grade 2, according to the Common Terminology Criteria for Adverse Events (CTCAE). The maximum CTCAE fatigue was grade 3. There have been no cases of RT pneumonitis to date. Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT delivery using standard methods.

Interstitial Pneumonitis after Treatment with Pemetrexed for Non-small Cell Lung Cancer

Pemetrexed is approved as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) with cisplatin and as a single agent for second-line treatment or for patients who show no disease progression after four cycles of platinum-based doublet induction chemotherapy as maintenance therapy. Pemetrexed has a modest toxicity profile and has not traditionally been regarded as a cause of interstitial pneumonitis. Here, we report on a rare case of pemetrexed-induced pneumonitis in a patient with NSCLC.

Ipilimumab-Induced Pneumonitis: A Case Report

Objective: To report a case of ipilimumab-induced pneumonitis in a patient with metastatic melanoma. Case Summary: A 74-year-old woman with metastatic melanoma presented to the emergency department with progressive shortness of breath and dyspnea of 1 week's duration following her third cycle of ipilimumab. Upon presentation, she was hypoxic, with oxygen saturation of 66% on room air. After stabilization, she was transferred to the inpatient unit where she was placed on broad-spectrum antibiotics (intravenous vancomycin, piperacillin/tazobactam, oral ciprofloxacin, and oral trimethoprim/sulfamethoxazole) and a high-dose corticosteroid (intravenous methylprednisolone 30 mg every 6 hours). Bronchoscopy was negative for infection, and results of blood, urine, and respiratory cultures were negative. Antibiotics were eventually stopped and the patient responded to a high-dose corticosteroid for probable ipilimumab-induced pneumonitis. Discussion: Ipilimumab is a recombinant, human monoclonal antibody that was approved for the treatment of metastatic melanoma. A black-box warning exists for immune-mediated adverse reactions, which can involve any organ system and are a result of T-cell activation and proliferation. The most common sites for these reactions are the gastrointestinal tract, skin, liver, and pituitary gland. The Naranjo probability scale indicated a probable relationship between the development of pneumonitis and ipilimumab therapy. Review of the literature through October 2012 did not yield any reports of single-agent, ipilimumab-associated pneumonitis in patients with metastatic melanoma. Infection was ruled out, and no other etiology was identified for the patient's acute symptoms. Furthermore, she responded quickly to a high-dose corticosteroid. Conclusions: Ipilimumab is associated with immune-mediated toxicities that can be severe or fatal. Prompt recognition and treatment of these reactions is necessary to prevent morbidity or mortality. This is the first reported case of single-agent, ipilimumab-associated pneumonitis in a patient with metastatic melanoma.

Hypersensitivity pneumonitis withMycobacterium aviumcomplex among spa workers

The New Mexico Department of Health (NMDOH) investigated the cause of two cases of hypersensitivity pneumonitis (HP) in spa maintenance workers with laboratory confirmed Mycobacterium avium complex (MAC). The investigation occurred in tandem with worker protection and swimming pool regulatory investigations by the New Mexico Environment Department at the spa where the workers were employed. The investigation was conducted in order to identify unreported cases, exposure source(s), and to prevent further worker exposure. NMDOH surveyed 57 spa employees about symptoms and exposures, categorized jobs according to self-reported exposure to water, and computed odds ratios for symptom reporting by exposure category. Environmental isolates from spa water and filter swabs were cultured and compared to patient isolates by the Environmental and Applied Microbiology Team, Centers for Disease Control and Prevention (CDC). Workers with the highest exposure reported more HP-like symptoms (OR = 9.6), as did intermediate exposure workers (OR = 6.5), compared to workers with no aerosolized water exposure. Two of 13 environmental isolates were closely related to one of the patient isolates. Workers were likely exposed during spray cleaning of cartridge filters in a poorly ventilated work space. Recommendations include inhibiting organism growth in spa systems, assuring the use of respiratory protection, and adequately ventilating work spaces where filters and equipment are cleaned.

Clinical characteristic analysis of 96 cases of hypersensitivity pneumonitis

To improve understanding of the clinical characteristics and diagnosis of hypersensitivity pneumonitis (HP). We retrospectively analyzed the clinical data, including clinical symptoms, laboratory tests, exposure, pulmonary function tests, chest CT imaging and cytological classification of bronchoalveolar lavage (BAL) of 96 patients with HP from Jan 2001 to Jun 2011 in Peking Union Medical College Hospital. We divided the patients into 2 groups: a pathologically-confirmed group and a clinically-suspected group. There were 58 females and 41 males. The median age at the diagnosis was 53 years. The most common exposures were low-molecular-weight chemicals (42.7%) and animal proteins (37.5%). Common clinical symptoms included dyspnea on exertion (90.6%) and cough (76.0%). Pulmonary function test showed diffusion abnormality (73.5%) and restrictive ventilatory impairment (59.7%). Chest CT scan revealed patchy or diffuse bilateral ground-glass opacities (64.6%), centrilobular nodules (21.9%), and air trapping (15.6%). Reticulation (45.8%), traction bronchiectasis (21.9%) and honeycombing(9.4%) were present in chronic HP. BAL lymphocyte counts > 0.2 and CD4/CD8 < 0.9 were more commonly seen in patients with a disease course of less than 1 year. The pathologically-confirmed group and the clinically-suspected group shared many similar characteristics including age at diagnosis, gender, clinical manifestation, pulmonary function impairments and imaging findings, but significant differences existed in certain parameters. In the pathologically- confirmed group, the duration of disease was longer (24 months vs 6 months, Z = -2.492, P = 0.013) and clubbed fingers were more common (23.4% vs 8.2%, χ(2) = 4.227, P = 0.040). Diffusion abnormality was present in more patients of this group (90.7% vs 44.0%, χ(2) = 35.219, P < 0.01). By CT scan, reticulation, traction bronchiectasis and honeycombing (57.5% vs 26.5%, χ(2) = 9.434, P < 0.01) were more evident as compared to the clinically-suspected group. The value of transbronchial lung biopsy for diagnosing HP was limited, with a positive result of only 8.2%. Surgical lung biopsy was needed in uncertain cases. The diagnosis of HP was difficult. In some cases a clinical diagnosis can be made by combination of history of exposure, CT manifestations and cell classification of BAL. For atypical cases a multi-disciplinary approach including pathologists, radiologists and pulmonologists is needed.

レース鳩飼育者に発症した急性鳥関連過敏性肺炎の１例

症例は54歳，男性．湿性咳嗽，血痰，労作時呼吸困難が出現し，健康診断で胸部X線写真上すりガラス影を指摘され近医を受診した．胸部CTで両側上肺優位に肺野濃度上昇を認めたため，精査目的で当院に入院となった．問診により，幼少時から自宅でレース鳩を飼育していることが判明し，鳥関連過敏性肺炎を疑った．気管支肺胞洗浄ではリンパ球の増加とCD4/8比の低下を認め，経気管支肺生検ではリンパ球浸潤を主体とする胞隔炎を認めた．また，患者が飼育している鳩血清および鳩糞と患者血清との間で行った沈降抗体反応は陽性であった．原因抗原からの隔離により肺病変が改善し，レース鳩を処分したのちに行った飼育小屋での環境誘発試験は陽性であった．以上からレース鳩飼育により急性発症した鳥関連過敏性肺炎と診断した．一般に本症は画像で線維化像を示す慢性型の場合が多い．本症例では，鳩の飼育数の増加によって抗原暴露量が著しく増加したことが急性型の発症を呈した原因と考えられた．

Methotrexate-Induced Pulmonary Toxicity

Methotrexate is a widely used medication with an array of recognized side effects. The present report describes a case of methotrexate-induced pneumonitis in a patient with psoriasis, and demonstrates the hallmark clinical and investigational findings that support this infrequently encountered diagnosis. The ensuing discussion reviews the pathogenesis, management and prevention of this adverse drug reaction.

Microorganisms in metalworking fluids: Current issues in research and management

The microbial contamination of water miscible metalworking fluids (MWFs) is a serious problem in metal industry. A good maintenance of MWF re-circulation systems can extend the lifetime of coolants and ensure the quality of the tools produced. In MWFs, as in the other water-based environments, microorganisms usually live in the form of biofilms, the communities of bacteria and fungi attached to the surface of sumps, metal parts and also to each other. Biofilms exhibit very high resistance to biocides. The effect of biocides that are used as additives to MWFs to control the growth of the bacterial and fungal microbiomes (microorganisms characteristic to the individual coolant system) have become the subject of research only in recent years. There are also only sparse reports on the impact of biocides on microorganisms growing in biofilms in MWF installations. Fast growing mycobacteria are important members of these biofilm communities. Their presence has recently been linked with the occurrence of cases of hypersensitivity pneumonitis, a serious respiratory disorder in the metal industry employees. The new, relatively fast and inexpensive techniques to assess the species diversity within MWF microbiomes and their population size should be developed in order to control the microorganisms' proliferation in MWFs and to diminish the occupational exposure to harmful bioaerosols in metal industry.

Zotarolimus-eluting stent-induced hypersensitivity pneumonitis

Zotarolimus-eluting stent-induced hypersensitivity pneumonitis

Lethal pneumonitis after docetaxel chemotherapy: Case report and review of the literature

Interstitial pneumonitis is a known, but uncommon adverse event during docetaxel therapy in cancer patients. We report the case of a patient with breast cancer who developed a severe, progressive pneu-monitis during dose-dense neoadjuvant chemother-apy with docetaxel. The condition was steroid resistant, and she died after 20 days on advanced ventilator therapy in the intensive care unit. The pneumonitis was complicated by reduced lung compliance, bilateral pneumothorax and severe hypercapnia and hypoxia. To our knowledge, this is the fi rst case of taxane-induced pneumonitis with a following autopsy report. We review the present lit-erature about the condition and discuss potential disease mechanisms.

Diagnostic approach to interstitial pneumonias in a single centre: report on 88 cases

BackgroundInterstitial pneumonias (IP) cover a broad spectrum of diseases. Open lung biopsies reveal histological patterns and suggest possible diagnoses. Complete clinical records are necessary for final diagnoses. Especially idiopathic interstitial pneumonias (IIP) according to the ATS/ERS classification can only be diagnosed under these predictions. The aim of this study was to compare the results of histological evaluations with the final diagnosis after interdisciplinary case evaluation.Patients and methods88 patients with interstitial pneumonia that underwent open lung biopsies were investigated. Histology and clinical records were available for review. Diagnosis was made in three steps: first on the sole basis of histology, second with clinical information given initially and third, on the basis of an interdisciplinary case evaluation.Results63 patients (72%) were diagnosed as idiopathic interstitial pneumonias according to ATS/ERS criteria. Further 10 (11%) cases of hypersensitivity pneumonitis, 7 (8%) Langerhans cell histiocytosis and 8 (9%) interstitial pneumonias of other known causes or associations were detected. Histological patterns alone agreed with the final diagnosis in 67%. In 82% histology and clinical information given to the pathologist could provide correct diagnosis. In the rest of cases, especially in non idiopathic interstitial pneumonias, an interdisciplinary case evaluation was needed.ConclusionsDiagnosis of interstitial pneumonias by open lung biopsies needs sufficient clinical information. Because of the overlap of histological patterns, an interdisciplinary case evaluation that includes at least one clinical expert and one pathologist with excellent expertise and the follow-up of the patients is necessary to find correct diagnosis in all cases.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5031706258025129

Salvage Treatment in Locoregional Recurrent Esophageal Carcinoma (EC) Using Intensity Modulated Radiation Therapy - Helical Tomotherapy (IMRT-HT)

Purpose/Objectives: Patients with locally advanced esophageal carcinoma are recommended to undergo treatment with radiation and chemotherapy, which may be followed by surgery in appropriate operative candidates. Radiation has traditionally been delivered with 3D conformal radiation therapy (3D CRT). This study is evaluating early outcomes and acute and late toxicity in patients treated with Intensity Modulated Radiation Therapy (IMRT) with concurrent chemotherapy. Materials/Methods: This is a retrospective review of 17 patients with esophageal carcinoma treated with IMRT and chemotherapy from 2008 2010. Pathology includes squamous cell and adenocarcinomas. Tumor sites include middle thoracic, lower thoracic and GE junction. Initial clinical stages are TX-T3, N0-3, and M0-1. All patients received at least one cycle of concurrent 5-fluorouracil with either cisplatin or oxaliplatin. IMRT dose was 50.4 Gy in 28 fractions prescribed to a target volume which included the tumor and regional lymphatics. All IMRT plans utilized coplanar beams in a 7-9 beam arrangement. Results: Median follow-up is 9 months (range, 4-20). Median patient age is 72 (range, 55-87). Sixteen patients received 50.4 Gy via an IMRT plan, and one received 25.2 Gy. Trimodality treatment was completed in 11 patients (65%). Surgery was either esophagogastrectomy or minimally invasive esophagectomy. Of the 11 patients who proceeded to surgery, 3 (27%) had a pathologic complete response, 7 (64%) had a partial response (PR) and 1 patient (9%) had stable disease. Of the 6 patients who received chemotherapy and IMRT alone, 2 patients had a clinical PR, 1 had disease progression, and 3 did not have follow-up data available. In the initial 17 patients, there were no local or regional recurrences, though 2 patients developed distant metastases. Twelve patients are alive at last follow-up. Of the 5 deaths, 2 were due to esophageal cancer, 1 from radiation complications, 1 from chemotherapy complications, and 1 from surgical complications. Acute CTCAE V4.0 grade 3 toxicities from concurrent chemotherapy and IMRT developed in the following patients: 2 esophagitis, 1 fatigue, 1 nausea/vomiting, 4 dehydration, 1 anemia, 1 thrombocytopenia and 5 neutropenia. Patients with grade 4 toxicities included 1 thrombocytopenia and 1 neutropenia. Four patients developed late grade 3 esophageal strictures. There was one grade 4 cardiac complication, and one grade 5 pleuro-esophageal fistula. There were no cases of radiation pneumonitis or ulcers. Conclusions: IMRT is a feasible treatment modality, which may be equally efficacious to 3D CRT for the treatment of esophageal carcinoma, and may offer fewer treatment complications, including a lower incidence of pneumonitis. Author Disclosure: K.V. Kowalchik: None. G. Kim: None. E. Johnson: None. N. Paryani: None. S. Ko: None.

Postmastectomy Hypofractionated and Accelerated Radiation Therapy With (and Without) Subcutaneous Amifostine Cytoprotection

Postmastectomy radiation therapy (PMRT) provides major local control and survival benefits. More aggressive radiation therapy schemes may, however, be necessary in specific subgroups, provided they are safely administered. We report the tolerance and efficacy of a highly accelerated and hypofractionated regimen (HypoARC). One hundred twelve high-risk patients who had undergone mastectomy received 10 consecutive fractions of 3.5 Gy in 12 days (thoracic wall and axillary/supraclavicular areas). Two consecutive additional fractions of 4 Gy were given to the surgical scar area (electrons 8-10 MeV) and 1 3.5-Gy fraction to the axilla (in cases with extensive nodal involvement). A minimum follow-up of 24 months (median, 44 months) was allowed before analysis. Of 112 patients, 21 (18.7%) refused to receive amifostine, the remaining receiving tolerance-based individualized doses (500-1000 mg/day subcutaneously). By use of a dose individualization algorithm, 68.1%, 11%, and 18.7% of patients received 1000 mg, 750 mg, and 500 mg/day of amifostine. Patchy moist skin desquamation outside and inside the booster fields was noted in 14 of 112 (12.5%) and 26 of 112 (23.2%) patients, respectively. No case of acute pneumonitis was recorded. High amifostine dose offered a significant skin protection. Within a median follow-up time of 44 months, moderate subcutaneous edema outside and within the booster thoracic area was noted in 5 of 112 (4.4%) and 8 of 112 (7.1%) cases, respectively. Intense asymptomatic radiographic findings of in field lung fibrosis were noted in 4 of 112 (3.6%) patients. Amifostine showed a significant protection against lung and soft tissue fibrosis. A 97% projected 5-year local relapse free survival and 84% 5-year disease-specific survival were recorded. Lack of steroid receptor expression, simple human epidermal growth factor 2 positivity, or triple negative phenotype defined higher metastasis rates but had no effect on local control. PMRT with HypoARC showed an excellent early and short-term late toxicity profile, and amifostine further reduced early and late radiation sequelae. Encouraging local control rates are obtained in high-risk subgroups.