Chemotherapy combined with radiotherapy for successful treatment of angioimmunoblastic T-cell lymphoma: a case report.

BACKGROUND: The incidence of angioimmunoblastic T-cell lymphoma is rare worldwide, and it has a poor prognosis. There is no proven or standard first-line therapy that works for the majority of patients with angioimmunoblastic T-cell lymphoma because of the rarity of this disease. The treatment and management are challenging for clinicians. CASE PRESENTATION: This report presents the diagnosis and treatment of a 65-year-old Chinese man who presented with cough and lymph node swellings in the left axillary region. The patient was diagnosed with angioimmunoblastic T-cell lymphoma. He underwent eight cycles of chemotherapy with CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone) followed by TOMO radiotherapy (helical tomotherapy, a kind of radiotherapy for cancer treatment using spiral computed tomographic scanning). After treatment, the therapeutic effects were evaluated by magnetic resonance imaging and computed tomography about every 3 months. The patient recovered well with no sign of tumor recurrence and no obvious severe treatment-related adverse effects. CONCLUSION: This treatment experience indicates an essential role for the combination of radiation therapy with CHOP, which may have a better prognosis than treatments without radiation therapy. But challenges warrant further validation in prospective studies.

Study of L-Asparaginase, Vincristine, and Dexamethasone Combined With Intensity-modulated Radiation Therapy in Early-Stage Nasal NK/T-Cell Lymphoma.

OBJECTIVES: Natural killer/T-cell lymphoma (NKTCL) is aggressive, and carries a poor prognosis worldwide. This retrospective study aimed to evaluate the clinical efficacy and safety of the LVD regimen (L-asparaginase, vincristine, and dexamethasone) combined with intensity-modulated radiation therapy (IMRT) for the treatment of early-stage nasal NKTCL in a Chinese population. METHODS: The clinical data were collected from patients treated between March 2010 and January 2017. Patients received LVD chemotherapy combined with IMRT, and were followed for 30 to 90 months. All received radiotherapy at the end of the first/second cycle of chemotherapy. The survival curves were generated by the Kaplan-Meier method. RESULTS: Among 94 patients who received 2 to 6 cycles (mean, 4 cycles) of treatments, 56 and 25 achieved complete and partial remission, respectively; 2 and 11 experienced stable disease and progressive disease. The overall objective response was 86.2%. Patients with elevated lactate dehydrogenase and skin invasion had a lower objective response rate. The progression-free survival rates at 1, 3, and 5 years were 90.3%, 73.5%, and 71.3%; the corresponding overall survival rates were 91.4%, 74.3%, and 74.3%. The main adverse events were myelosuppression (63.8% grades I to II, 12.8% grade III), gastrointestinal symptoms (63.8% grades I to II), hepatic lesion (55.3% grades I to II), hypoproteinemia (46.8% grades I to II), skin allergies (77.7% grades I to II, 3.2% grade III), and oral mucosal lesions (44.7% grades I to II, 33% grade III). No severe pancreatitis, anaphylaxis, or toxicity-related death was observed. CONCLUSION: In patients with early-stage nasal NKTCL, our LVD-IMRT regimen produced excellent, durable therapeutic benefit in most patients, with acceptable toxicity and no acute mortality.

[Clinical observation of LOP chemotherapy combined with radiotherapy in the treatment of early nasal NK/T cell lymphoma].

Objective:To investigate the efficacy and safety of LOP（asparaginase + vincristine + dexamethasone） chemotherapy combined with radiotherapy in patients with nasal NK/T cell lymphoma. Method:Sixty patients with nasal NK/T cell lymphoma admitted to our hospital from February 2012 to February 2016 were selected as the study subject. They were randomly divided into group A and group B, 30 cases in each group. All patients were treated with combined chemotherapy and IMRT（intensity modulated conformal radiotherapy）. The LOP regimen was used in group A and the CHOP（cyclophosphamide + pirarubicin + vincristine + dexamethasone） regimen was used in group B. The short-term efficacy, long-term efficacy and adverse reactions of the two groups were compared. Result:The clinical manifestations of 60 patients mainly included nasal obstruction（81.67%）, accompanied by fever, headache, nosebleed and runny nose. Forty-one patients（68.33%） had only one site of lesion, and 21 patients（35.00%） had multiple sites of lesions. In terms of total remission rate, it was significantly higher in group A than that in group B（93.33% vs. 66.67%, P<0.05）. In terms of adverse reactions, the incidence of bone marrow suppression, gastrointestinal reaction and low-protein reaction was significantly lower in group A than that in group B（P<0.05）. Three patients died in group A and 11 patients died in group B during the 3-year follow-up. The 3-year survival rate of group A was higher than that of group B（P<0.05）. Conclusion:Compared with CHOP+IMRT regimen, the LOP+IMRT regimen for nasal NK/T-cell lymphoma patients resulted in higher overall remission rate, survival rate and lower adverse reactions, so it is worth in clinical promotion.

Beneficial effect of consolidative radiotherapy for patients with lymphoma and skeletal involvement.

The objectives of this study were to analyze the clinical features of patients with bone involved lymphoma and identify the prognostic factors and to explore the optimized treatment strategy for bone involved lymphoma.A total of 1948 patients with lymphoma in our cancer center from September 2006 to October 2017 were retrospectively evaluated. Among these, 109 patients with skeletal involvement in lymphoma were enrolled. According to the pathologic subtypes, the patients were divided into 3 subgroups: classic Hodgkin lymphoma (cHL), B-cell non-Hodgkin lymphoma (B-NHL), and T-cell non-Hodgkin lymphoma (T-NHL). The clinical characteristics and overall survival (OS) of 3 groups of patients were reviewed, and the prognostic factors were analyzed.There were 9 (3 unifocal, 6 multifocal) patients with primary bone lymphoma. The 5-year OS of cHL, B-NHL, and T-NHL patients was 88.24%, 54.09%, and 61.58%, respectively. Advanced stage, elevated lactate dehydrogenase (LDH), age above 60, high International Prognostic Index score, and treatment without radiotherapy for the bone involved were significant poor prognostic factors for OS of all patients in univariate analysis. There was a trend toward better OS not only in limited-stage but also in advanced-stage patients with radiotherapy for the bone involved compared with the patients without radiotherapy. Elevated LDH level and age above 60 were the independent unfavorable prognostic factor in multivariate analysis.Elevated LDH level and age above 60 predict the poor prognosis of patients with bone involvement. The potential for long-term survival suggests that additional consolidative radiotherapy for the site of skeleton involvement may have a better chance of long-term success.

90Y-NM600 targeted radionuclide therapy induces immunologic memory in syngeneic models of T-cell Non-Hodgkin's Lymphoma.

Finding improved therapeutic strategies against T-cell Non-Hodgkin's Lymphoma (NHL) remains an unmet clinical need. We implemented a theranostic approach employing a tumor-targeting alkylphosphocholine (NM600) radiolabeled with 86Y for positron emission tomography (PET) imaging and 90Y for targeted radionuclide therapy (TRT) of T-cell NHL. PET imaging and biodistribution performed in mouse models of T-cell NHL showed in vivo selective tumor uptake and retention of 86Y-NM600. An initial toxicity assessment examining complete blood counts, blood chemistry, and histopathology of major organs established 90Y-NM600 safety. Mice bearing T-cell NHL tumors treated with 90Y-NM600 experienced tumor growth inhibition, extended survival, and a high degree of cure with immune memory toward tumor reestablishment. 90Y-NM600 treatment was also effective against disseminated tumors, improving survival and cure rates. Finally, we observed a key role for the adaptive immune system in potentiating a durable anti-tumor response to TRT, especially in the presence of microscopic disease.

Subcutaneous Panniculitis-Like T-Cell Lymphoma With Granulomas as the Predominant Feature.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma preferentially localized in the subcutaneous adipose tissue and composed of cytotoxic T cells with an α/ß immunophenotype. The neoplastic T cells can be variably admixed with other inflammatory cells, including histiocytes, which can rarely form noncaseating granulomas. We present a case of SPTCL in which granulomas are the predominant feature, composing 75%-80% of the inflammatory infiltrate. The top differential diagnoses included infectious and autoimmune etiologies. However, special stains for microorganisms were negative, and immunohistochemical analysis of the atypical lymphocytes showed a CD3, CD8, TIA-1+, T-cell receptor (TCR) beta+, and CD4 infiltrate with a high Ki67 proliferation index of approximately 30%. TCR gene rearrangement studies by polymerase chain reaction with confirmation by high-throughput sequencing were necessary to exclude an autoimmune etiology, specifically lupus erythematosus panniculitis. To the best of our knowledge, only 1 other case of SPTCL with prominent granulomas has been reported in the literature. It is important for dermatopathologists to recognize this presentation of SPTCL. SPTCL with predominant granulomas should be included in the differential diagnosis of granulomatous panniculitis along with infectious and autoimmune panniculitides as well as other granulomatous lymphomas.

A clinical example of extreme dose exposure for an implanted cardioverter-defibrillator : Beyond the DEGRO guidelines.

INTRODUCTION: Considering that the number of malignant diseases in patients over 65 years of age is increasing, it often occurs that patients who carry a cardiac implanted electronic device must undergo radiotherapy. Ionizing radiation can disturb the function of the implantable cardioverter-defibrillator (ICD). As a result of this, an update of the DEGRO/DKG guidelines for radiotherapy of this patient group has been published. METHODS: We report the case of a patient with an ICD and T­lymphoblastic lymphoma with cardiac involvement, who received i.a. a total body irradiation with 8 Gy followed by a consolidating radiotherapy of the pericardium with 14 Gy as well as additional radiotherapy courses after consecutive recurrences. For the purposes of the treatment, the antitachyarrhythmia (ATA) therapy was deactivated and temporarily replaced through a life vest. RESULTS: According to the current DEGRO guidelines for irradiation of patients with cardiac implanted electronic devices, a categorization of the patient in the "high-risk" group was made. Furthermore, regular telemetric checks of the ICD device were performed before and after treatment. Despite unavailable declaration of the manufacturer regarding the cumulative tolerable dose and DEGRO recommendation for a cumulative dose <2 Gy, the aftercare was unproblematic and normal values were assessed for all relevant ICD parameters, despite a cumulative dose >10 Gy in the device. CONCLUSION: This case shows that if the cardiac implanted electronic devices are not directly irradiated und the energy used is reduced to 6 MV, irradiation-induced damage is less likely and can possibly be prevented.

Applying orthodontic tooth extrusion in a patient treated with bisphosphonate and irradiation: a case report.

Bisphosphonates and irradiation are useful medical treatments, but can often cause oral complications such as medication-related oral necrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) during oral surgery, including tooth extraction. Therefore, we should take all risks into consideration carefully before choosing dental treatment for patients with a medical history of such therapies. A 55-year-old woman who underwent cord blood transplantation to treat extranodal natural killer T (NK/T) cell lymphoma (nasal type IVB) had a medical history of bisphosphonate and irradiation treatments. We treated her residual tooth root by applying orthodontic extrusion to avoid extraction and successfully restored the tooth. Application of an orthodontic tooth extrusion technique for conservative treatment of a residual tooth is a useful means of avoiding MRONJ or ORN in patients who have a medical history of bisphosphonate and irradiation treatments.

Clinical characterization and outcome of primary bone lymphoma: a retrospective study of 61 Chinese patients.

Primary bone lymphoma(PBL) is a rare disease. To assess the clinical characteristics, outcome, and prognostic factors of this entity in Chinese population, we retrospectively analyzed 61 PBL patients initially treated in our institution between 1997 and 2014. The median age was 45 years. The most common histological subtype was diffuse large B-cell lymphoma (DLBCL) (55.7%), followed by T-cell lymphoma (18.0%). All patients underwent systemic chemotherapy as initial treatment while 24 patients (39.3%) were additionally treated with radiotherapy. The 5-year overall survival (OS) and the 5-year progression-free survival (PFS) rates of 57 cases with completed follow-up were 52.3% and 40.1%, respectively. In further analysis of the primary bone DLBCL (PB-DLBCL) subgroup, the 5-year OS and PFS rates were 53.0% and 47.0%, and a multivariable analysis revealed that baseline Eastern Cooperative Oncology Group (ECOG) score and response to initial treatment (complete remission versus no complete remission) were independent prognostic factors for both OS and PFS. The proportion of T-cell lymphoma is higher in China than in western populations. High baseline ECOG scores (≥2) and unachieved CR in initial therapy were factors for poor PB-DLBCL prognosis. The role of radiotherapy and rituximab in PLB therapy remains to be confirmed in further investigation.

Managing Patients with Cutaneous B-Cell and T-Cell Lymphomas Other Than Mycosis Fungoides.

Cutaneous lymphomas (CL) are a heterogeneous group of neoplasms characterized with clinical and histopathological variation, as well as overlap with benign dermatoses. Diagnosis and treatment of CLs is challenging and often requires a multidisciplinary approach. However, prognostic knowledge of these conditions and awareness of treatment options can help optimize appropriate use of available regimens, thereby improving care for patients. Here, we review the most recent literature and outline treatment themes for managing patients with cutaneous B-cell and T-cell lymphomas other than mycosis fungoides.

Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy.

Monitoring mice exposed to carbon ion radiotherapy provides an indirect method to evaluate the potential for second cancer induction in normal tissues outside the radiotherapy target volume, since such estimates are not yet possible from historical patient data. Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume (average linear energy transfer = 13 keV x µm(-1)) during patient radiotherapy protocols. The mice were monitored for the remainder of their lifespan, and a large number of T cell lymphomas that arose in these mice were analysed alongside those arising following an equivalent dose of 137Cs gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikzf1, Pten, Trp53 and Bcl11b genes, we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. If such large interstitial chromosomal deletions are a characteristic lesion of carbon ion irradiation, even when using the low linear energy transfer radiation to which normal tissues are exposed in radiotherapy patients, understanding the dose-response and tissue specificity of such DNA damage could prove key to assessing second cancer risk in carbon ion radiotherapy patients.

Vocal Fold Paralysis as a Delayed Consequence of Neck and Chest Radiotherapy.

OBJECTIVE: To describe a series of cases of vocal fold paralysis years after radiation therapy, including presentation, clinical course, and treatment. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: A review of 8 years of patient records yielded 10 patients (8 male and 2 female; average age 57 years [range, 29-76 years]) with vocal fold paralysis and a history of radiation therapy to the head, neck, or mediastinum. These patients did not have other possible etiologies of vocal fold paralysis. Demographic, diagnostic, clinical course, and treatment data were collected. RESULTS: On average, 21 years (range, 1-27 years) elapsed between completion of radiation and presentation with vocal fold paralysis. Original pathologies included Hodgkin lymphoma (5), squamous cell carcinoma of the head and neck (4), and peripheral T-cell lymphoma (1). Eight patients had unilateral left vocal fold paralysis, and 2 had bilateral neuropathy; none recovered spontaneously. All patients had dysphonia, and nearly all patients also complained of dysphagia. Six elected not to be treated. Four underwent injection augmentation with resolution of voice complaints. CONCLUSIONS: Radiation therapy has the potential to cause laryngeal neuropathy years to decades after treatment. The potential for recovery is low, but injection augmentation can relieve symptoms. Development of contralateral neuropathy and altered tissue response are considerations in treatment.

Intraoperative high-dose rate of radioactive phosphorus 32 brachytherapy for diffuse recalcitrant conjunctival neoplasms: a retrospective case series and report of toxicity.

IMPORTANCE: Adjunct treatments for conjunctival malignancies are needed when standard therapy provides limited benefits or fails. OBJECTIVE: To describe the results of patients with diffuse conjunctival neoplasms treated with radioactive phosphorus 32 (32P)-impregnated flexible film. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series between January 1, 2010, and January 1, 2013, was conducted at Memorial Sloan-Kettering Cancer Center, a tertiary referral center. The study was conducted on 7 eyes of 6 patients treated for diffuse conjunctival squamous cell carcinoma, sebaceous carcinoma, or lymphoma that had recurrent or residual disease after primary treatment. INTERVENTIONS: Patients underwent mapping biopsies and detailed conjunctival drawings to delineate the pathologic extent of the disease. The brachytherapy film used for treatment was the RIC Conformal Source Model 100 (RIC-100, RI Consultants). The RIC-100 is a flexible, thin (approximately 0.5-mm) film made of a polymer chemically bound to 32P. The radioactive 32P film was placed intraoperatively, allowed to stay in place until the prescription dose was reached, and then removed. The median dose at the prescription point (1 mm from the surface of the film) was 15 Gy (range, 5-17 Gy). MAIN OUTCOMES AND MEASURES: Patients were tested for best-corrected visual acuity, recurrence-free survival, and adverse events scored by using the Adult Comorbidity Evaluation-27 scale. RESULTS: Between 2010 and 2013, 7 eyes of 6 patients were treated. The median age of patients was 70 years. All patients had a recurrent or persistent neoplasm. Four patients with squamous cell carcinoma, 1 with sebaceous carcinoma, and 1 with metachronous bilateral lymphomas were treated. The median treatment time was 19 minutes (range, 10-52 minutes). The median follow-up was 24.9 months (range, 3.1-38.2 months). Recurrence-free survival 24 months after brachytherapy was 75% (95% CI, 19-89.1). Two moderate adverse events and 1 severe adverse event occurred. Visual acuity was stable or improved in 5 of the 7 eyes (ie, better than 20/70 in the 5 patients who retained their treated eye). CONCLUSIONS AND RELEVANCE: Our results show the use of an intraoperative high-dose rate of 32P brachytherapy in selected cases of recalcitrant diffuse conjunctival neoplasms. This technique offers a novel adjunct in the treatment of these cancers. Further follow-up and study are warranted.

A phase II study of ifosfamide, methotrexate, etoposide, and prednisolone for previously untreated stage I/II extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial of the Korean Cancer Study Group.

BACKGROUND: Combination chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma (NTCL). METHODS: Forty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m(2) on days 1-3; methotrextate 30 mg/m(2) on days 3 and 10; etoposide 100 mg/m(2) on days 1-3; and prednisolone 60 mg/m(2) per day on days 1-5) followed by involved field radiotherapy (IFRT). RESULTS: Overall response rates were 73% (complete remission [CR] in 11 of 41 evaluable patients [27%]) after IMEP chemotherapy and 78% (CR 18 of 27 evaluable patients [67%]) after IMEP followed by IFRT. Neutropenia and thrombocytopenia were documented in 33 patients (75%) and 7 patients (16%), respectively. Only 8 patients (18%) experienced febrile neutropenia. Three-year progression-free survival (PFS) and overall survival (OS) were 66% and 56%, respectively. High Ki-67 (≥70%) and Ann Arbor stage II independently reduced PFS (p = .004) and OS (p = .001), respectively. CONCLUSION: Due to the high rate of progression during IMEP chemotherapy, IFRT needs to be introduced earlier. Moreover, active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL.

SIE-SIES-GITMO guidelines for the management of adult peripheral T- and NK-cell lymphomas, excluding mature T-cell leukaemias.

BACKGROUND: In order to promote widespread adoption of appropriate clinical practice, the Italian Society of Hematology (SIE), and the affiliate societies SIES (Italian Society of Experimental Hematology) and GITMO (Italian Group for Bone Marrow Transplantation) established to produce guidelines in the most relevant hematological areas. In this article, we report the recommendations for management of T/NK-cell lymphomas, excluding mature T-cell leukaemias. DESIGN: By using the Grades of Recommendations, Assessment, Development and Evaluation (GRADE) system, we produced evidence-based recommendations for the key clinical questions that needed to be addressed by a critical appraisal of evidence. The consensus methodology was applied to evidence-orphan issues. RESULTS: Six courses of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone (CHOEP) chemotherapy were recommended for first-line therapy of patients with nodal, intestinal or hepatosplenic T-cell lymphomas (evidence: low; recommendation: do, weak). Except for ALK+ anaplastic large-cell lymphoma and elderly unfit patients, consolidation with high-dose chemotherapy was recommended (evidence: low; recommendation: do, weak). 50 Gy radiotherapy was the recommended first-line therapy for localized extranodal T/NK-cell lymphoma nasal type (evidence: low; recommendation: do, strong), while l-asparaginase-containing chemotherapy regimens were recommended for patients with systemic disease (evidence: very low; recommendation: do, strong). CONCLUSION: In adult T/NK-cell lymphomas, GRADE methodology was applicable to a limited number of key therapeutic issues. For the remaining key issues, due to lack of appraisable evidence, recommendations was based on consensus methodology.

Primary distal femur T-cell lymphoma after allogeneic haematopoietic stem cell transplantation for chronic myeloid leukaemia: a rare case report and literature review.

Post-transplant lymphoproliferative disorders originating from T lymphocytes are a rare complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT) that are not usually associated with Epstein-Barr virus infection. A male patient diagnosed at the age of 15 years with chronic myeloid leukaemia (in the chronic phase) was initially treated with oral hydroxyurea. The disease entered an accelerated phase when the patient was 22 years old. Complete remission was achieved after one course of homoharringtonine and cytarabine. The patient then underwent human leucocyte antigen-matched sibling donor allo-HSCT. Just over 6.5 years after the allo-HSCT, a second primary tumour was located in the distal femur and diagnosed as T-cell non-Hodgkin's lymphoma (stage IV, group B). This was treated with various chemotherapy and radiotherapy regimens, but the outcomes were poor and the disease progressed. The T-cell lymphoma invaded many sites, including the skeleton, spleen and skin, and the patient died within 8 months of the diagnosis. This current case report highlights the need for the early detection and prevention of subsequent primary malignancies after allo-HSCT.

A prospective phase II study of L-asparaginase- CHOP plus radiation in newly diagnosed extranodal NK/T-cell lymphoma, nasal type.

PURPOSE: To explore the efficacy and safety of L-asparaginase in newly-diagnosed extranodal nature killer (NK)/T -cell lymphoma (ENKTL), we conducted a prospective phase II study of L-asparaginase, cyclophosphamide, vincristine, doxorubicin and dexamethasone (CHOP-L) regimen in combination with radiotherapy. PATIENTS AND METHODS: Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment. Treatment included 6-8 cycles of CHOP-L (cyclophosphamide, 750 mg/m(2) day 1; vincristine, 1.4 mg/m(2) day 1 (maximal dose 2 mg), doxorubicin 50 mg/m(2) day 1; dexamethasone 10 mg days 1-8; L-asparaginase 6000 u/m(2) days 2-8). Radiotherapy was scheduled after 4-6 cycles of CHOP-L regimen, depending on stage and primary anatomic site. The primary endpoint was complete response (CR) rate. RESULTS: A total of 38 eligible patients were enrolled. The median age was 40.5 years (range, 15 to 71 years). Their clinical characteristics were male to female ratio, 24:14; Ann Arbor stage I, 20; II, 11; III, 3; IV, 4. CR and overall response rates were 81.6% (95% CI, 69.3% to 93.9%) and 84.2%, respectively. With a median follow-up of 25 months, the 2-year overall survival, progression-free survival and disease-free survival rates were 80.1% (95%CI, 73.3% to 86.9%), 81% (95%CI, 74.5% to 87.5%) and 93.6% (95%CI, 89.3% to 97.9%), respectively. The major adverse events were myelosuppression, liver dysfunction, and digestive tract toxicities. Grade 3 to 4 leukopenia and neutropenia were 76.3% and 84.2%, respectively. No treatment-related death was observed. CONCLUSION: CHOP-L chemotherapy in combination with radiotherapy is a safe and highly effective treatment for newly diagnosed ENKTL.

Combined therapy in untreated patients improves outcome in nasal NK/T lymphoma: results of a clinical trial.

Nasal NK/T-cell lymphoma is a rare presentation of T-cell lymphoma in USA and in Europe, but is the most common presentation in Latin America. The lymphoma is associated with a worse prognosis even in the early stage. Until now, a better treatment has not been determined. We performed a prospective, open-label, controlled clinical trial to assess the efficacy and toxicity of the most common treatment options. We treated 427 patients, of whom 109 patients received radiotherapy (RT), 116 patients received chemotherapy (C), and 202 patients received combined therapy (CT), which were balanced according to stage and prognostic factors. Complete response was achieved in 91 % (95 % confidence interval CI 88-102 %) in CT arm 69 % (95 % CI 61-75 %) in RT arm; and 59 % (95 % CI 48-64 %) in C arm (p < 0.01). A progression-free disease was 91 % (95 % CI 83-96 %); 78 % (95 % CI 69-86 %); and 40 % (95 % CI 32-46 %), respectively (p < 0.01). Actuarial curves of overall survival at 5 years were as follows: 86 % (95 % CI 81-90 %), for CT; 64 % (95 % CI 59-70 %) for RT; and 45 % (95 % CI 39-51 %) for C (p < 0.001). Toxicity was mild and well tolerated. To our knowledge, this is the first controlled clinical trial, with a large number of patients and longer follow-up. Thus, we conclude that CT is the best therapeutic option in this setting of patients.

Intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for stage I-II natural killer/T-cell lymphoma nasal type: dosimetric and clinical results.

BACKGROUND: This study was to compare radiotherapy treatment planning and treatment outcomes following three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in stage I-II natural killer (NK)/T-cell lymphoma. METHODS: The cases of 94 patients with stage I-II NK/T-cell lymphoma, nasal type in the upper aerodigestive tract who treated between May 2005 and Dec 2008 were reviewed. These patients received radiotherapy with or without induction chemotherapy. Definitive radiotherapy was conducted using 3DCRT in 47 patients and IMRT in the other 47 patients with a regional field and a total dose of 50 Gy. Dosimetric pmeters of radiation treatment plans, local control probability (LCP), overall survival (OS), and toxicities were analyzed and compared between 3DCRT and IMRT. RESULTS: From the dosimetric analysis, IMRT demonstrated significantly better dose coverage and homogeneity than 3DCRT. However, after a median follow-up of 46 months, IMRT was not associated with improvements in 4y-OS (80.9% for 3DCRT vs. 82.7% for IMRT, p=0.87) or 4y-LCP (86.3% for 3DCRT vs. 88.9% for IMR p=0.85). Of the 18 patients who received cervical lymph node irradiation, those in the IMRT group received a lower mean parotid dose. Furthermore, at-risk organs were strictly kept within the safe dose range in both groups, and no severe late toxicity was observed. CONCLUSIONS: IMRT provided better dose coverage than 3DCRT, although it failed to provide LCP and OS benefits. Definitive radiotherapy with a regional field and a total dose of 50 Gy is efficient and safe for NK/T-cell lymphoma using either IMRT or 3DCRT. However, IMRT may have the potential to reduce parotid gland hypofunction following cervical irradiation.