| 1.Background and ObjectivesExtranodal, nasal type NK/T cell lymphoma was a rare type of non-hodgkin’s lymphoma(NHL), accounting for about 2%-10%. Among NHL, much more malignant cells derived from mature NK cells and a few from NK like T cells, all of which were called NK/T cell lymphoma. Most primary tumors located in the upper neck(the nose and throat), very few patients with primary beyond nasal, such as gastrointestinal tract, lungs, skin and so on. Few clinical cases of early disease were characterized with systemic spread(IV) but without involvement of nasal cavity. Its pathological performance was unique that pleomorphic lymphocytes were centered on blood vessel, lymphoma cell infiltration induced angiolysis and tissue necrosis.Extranodal, nasal type NK/T cell lymphoma was sensitive to radiation. As for early stage(stage I, stage IE), radiotherapy alone could receive a better therapeutic effect, and more, high dose radiation was related with high rate of long term survival(local dosage more than 5000cGy). However, because of high metastasis rate for advanced cases, concurrent chemotherapy was necessary.The CHOP regimen(anthracycline-based drugs), used in the treatment of non-hodgkin’s lymphoma, displayed insensitivity for nasal type NK/T cell lymphoma and occurred rapid recurrence after a short-term remission. Multiple studies showed 5 years survival rate only 7% to 25%. But in our study, GDP(gemcitabine, cisplatin, prednisone) regimen conducted as a new first-line chemotherapy options for extranodal NK/T cell lymphoma.Hyperthermia used physical energy caused by a set of capacitance field heat source to act on tissues, produced ion movement and thermocouple dipole rotary motion in the human body in order to treat and kill tumor cells.For early stage nasal type NK/T cell lymphoma, it is still a controversial topic that radiotherapy and hyperthermia combined with chemotherapy, but which is the main and preferred treatment in the clinical settings. The author retrospectively compared the different treatment effects between radiotherapy and chemoradiotherapy(GDP regimen) combined with hyperthermia, respectively. 2.Object and MethodsIn this study,patients were selected from September 2008 to August 2011 in our radiotherapy oncology department and oncology department,and all patients diagnosed of non-hodgkin’s lymphoma- nasal NK/T cell lymphoma by pathological and immunohistochemical diagnosisInclusion criteria: 1, all patients were diagnosed by our hospital pathological department or the association of provincial pathological and the first diagnosis of non-hodgkin’s lymphoma- nasal type NK/T cell lymphoma. All tumor sections obtained before treatment and subjected to immunohistochemistry(IHC) to detect, all sections with CD56(+), CD3(+), CD2(+), CD43(+), in situ hybridization: EBER(+), all the immunohistochemical results display no B cell antigen expression, such as of CD19, CD20, CD22 negative, ki- 67(10%-80%); 2, patients not treated with radiation and chemotherapy, ECOG score 2 points or less; 3, no obvious contraindication of chemotherapy: 95 g/L or higher hemoglobin, neutrophil count absolutely 2.0 x 109 / L, blood platelet ≥100 x 109 / L, glutamic-pyruvic transaminase(ALT) and glutamic oxalacetic transarninase(AST) less 1.5 times the upper limit of normal, serum total bilirubin(TBIL) acuities were 2.0 times the upper limit value, the normal serum creatinine(CREA) 1.8times the upper limit value, the normal serum albumin(propagated) or 30 g/L, original(FIB) normal serum fiber protease; 4, we can measure the lesion size in one imaging data at least; 5, eliminate conflicts with the solution by other serious diseases: basic structure and function of heart and lung are normal; 6, there is no other antitumor drugs with treatment: such as traditional Chinese medicines(including antitumor use class(traditional), biological immune therapy, etc.), but we can use bisphosphonates drugs to treat hypercalcemia and bone metastases; 7, the patients have certain ability of word recognition can understand the situation of this study and signed informed consent.Exclusion criteria: 1, case information are not completely; 2, B cell antigen expression by IHC; 3, patients with severe heart cerebrovascular disease(such as heart failure, atrial fibrillation, arrhythmia, angina, myocardial infarction, etc.); 4, allergic to the drugs fo the the research, such as allergic constitution or ignorance of urticaria, etc.), or metabolic disorders such as liver and kidney dysfunction or failure, etc.); 5, patients with any uncontrolled medical disease(such as the activity of pulmonary tuberculosis, replication of hepatitis and uncontrolled diabetes, etc.); 6, patients who suffered from other malignant tumors or have a primary or secondary tumor invasion of the central nervous system(such as brain tumor, brain metastases, crest marrow metastasis, etc.); Have obvious contraindications of chemotherapy, radiation therapy and thermal therapy; 7, have the peripheral nervous system disorders or with mental disorders(such as Parkinson’s disease, depression and other classes); have no ability to bear the laws and regulations, and the patients may impact study continues recognized by clinical medicine or medical ethics committee; 8, patients participate in other clinical researchers at the same time; patients who treatment with other antineoplastic drugs, and refused to provide blood samples. The treatment of this study: the deep heat radiation GDP plan or simple radiotherapy, deep heat treatment of the patients.82 patients were selected ultimately by random and strictly filtrating according to the inclusion and exclusion criteria, including 37 female patients and 45 male patient, the median age 42. The initial symptoms in the patients are: continuous high fever, stuffy nose, pharynx pain and nose with blood; and outside nasal symptoms such as: oral and maxillofacial region, parotid gland area, double or single eye swelling and symptoms of cervical lymph node enlargement(I- VI). Performance for a local nasopharyngeal cavity ulcer, even perforation, nasal bleeding, bad breath symptoms. Clinical stage based on medical history, physical examination and other examinations(nasal SCT, PET- CT, chest SCT, bone wear) assay; All patients confirmed the tumor lesion and size range before treatment by using through nasal cavity and sinuses SCT and MRI or PET- CT. And the clinical stage used Ann Arbor principle and the revised principle of cancer hospital, Chinese academy of sciences. 37 patients are staging I, 33 patients are Ⅱ, 10 patients are Ⅲand 2 patients are Ⅳ. All patients are divided into two groups according to the different treatment: experimental group(43 patients with deep heat radiation GDP) and the control group(39 patients with radiotherapy combined with deep heat therapy).All patients in two groups positioned by 64 layers SCT positioning machine(Germany’s Siemens), drawing target outline based on tumor radiotherapy standard, referenced all imaging data, divided into GTV, CTV. Physicist work out plans with 3D-TPS planning system; Radiotherapy using IMRT external exposure(USA- Varian) or(Sweden- Elekta) 6-9 external beam radiation, DT: 200 cGy/wild/time /day, total 50 Gy, deep heat treated with topical treatment, for 40 to 50 minutes, the heat temperature is 41-43 ℃, 2 times/Week; Patients in the experimental group treated with GDP solution(GEM and DDP, prednisone, dosage according to the NCCN guidelines, 1, 6 d cycle, the GEM d1, DDPd1- d5, prednisone piece of 100 mg QD PO, rest 2 d, d8 use GEM, interval of 25 d- 28 d, amuse(4-6 course) before the date of deep heat therapy combined with radiotherapy; The patients in control group treated with deep heat radiation combined with radiation therapy, and the solution of deep heat treatment and radiation therapy are same to the solutions in experimental group. All patients were follow-up for half a year after treatment, and evaluate the curative effect. 3.Results3.1 Short term effect: all 82 patients completed the treatment and the curative effect was evaluated in complete or within 3 months after the treatment. In experimental group, 23 complete response cases(complete remission rate: 53.5%), 18 partial response cases, 1 stable case and 1 progression case were observed. In contrast group, there were 12 complete response cases(complete remission rate: 30.8%), 24 partial response cases, 1stable case and 2 progression cases. There was significant difference between the two groups in terms of complete remission rate(53.5% vs. 30.8%, p<0.05)3.2 Toxicity evaluation was conducted in complete or within 3 months after the treatment. Compared to contrast group, patients in experimental group occurred more leucopenia and thrombocytopenia(p<0.05), however, no statistical difference was observed in digestive system, skin and neck edema reaction(p>0.05).3.3 The long-term curative effect: by deadline of 5-year follow-up, there were 18 deaths in experimental group and 13 in contrast group. The cause of death included local recurrence, metastasis and severe complications, etc. Experimental group manifested 56.3 months of average survival time and 37.3 months of median survival time. But for contrast group, 57.6 months of average survival time and 36.1 months of median survival time. There was no obvious difference in 5-year overall survival(experimental group vs. contrast group= 58.1% vs. 66.7%, p>0.05). Similar result was obtained for progression-free survival(experimental group vs. contrast group= 39.5% vs. 35.9%, p>0.05) 4.ConclusionCompared to radiotherapy alone, chemoradiotherapy combined with hyperthermia showed a better complete response rate but heavily adverse effects. There was no significant difference in long-term survival for the two treatments. Our study provide important treatment reference for patients with nasal type NK/T cell lymphoma to improve recent complete remission. |
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