临床研究 Neo-adjuvant Docetaxel and Cisplatin Followed by Concurrent Docetaxel and Cisplatin with Intensity-modulated Radiation Therapy in Treatment of Locally Advanced Recurrent Nasopharynx Cancer
|School||Guangzhou Medical College|
|Keywords||Recurrent nasopharyngeal carcinoma Intensity-modulated radiotherapy Local recurrence Reirradiation induction chemotherapy Concurrent chemoradiotherapy cisplatin Docetaxel|
BACKGROUND&OBJECTIVENasopharyngeal carcinoma (NPC) is generally sensitive to radiation and chemotherapy, and excellent loco-regional control can be achieved by chemo radiotherapy. loco-regional relapse, however, still represents a major failure pattern in NPC. Aggressive salvage treatment of local recurrence of NPC is usually recommended and a significant proportion of patients with limited or early relapse can still achieve long-term survival after nasopharyngectomy, brachytherapy and radiosurgery. Since violations of a wide range of neoplasms Patients with advanced local recurrence of nasopharyngeal carcinoma (NPC) are not amenable to these salvage treatment and have a poor prognosis commonly. Retreatment by external radiotherapy is frequently the only curative option but results are usually poor. treatment planning is often difficult and poses a special challenge to radiation oncologists. The advent of intensity-modulated radiotherapy (IMRT) has offered the potential of improved target conformation and sparing of critical structures. IMRT is particularly suitable for NPC due to the irregular target volume and proximity of critical structures. Early studies have showed improved dose distribution and treatment results using IMRT for newly diagnosed NPC. Clinical studies have showed IMRT also improved the treatment outcome in patients with local recurrence. the shrinkage of tumor before reirradiation would facilitate radiotherapy planning and delivery, which is important in the setting of retreatment of NPC with a narrow therapeutic ratio. This could in turn lead to improvement of target dose distribution and coverage, especially in rT3–4 stage in which sparing of adjacent critical structures was more difficult.This study was conducted to evaluate the benefits of adding induction chemotherapy with cisplatin and Docetaxel before reirradiation followed by concurrent chemoradiotherapy for locally advanced recurrent NPC.METHODS AND MATERIALSThirty-one patients with locally advanced recurrent nasopharynx carcinoma not amenable to brachytherapy or surgery were enrolled between March.1,2008 and October.31,2009 in GuangZhou medical college affiliated hospital of tumor .Median age was 46.5 (29-60)years and Median time from first course of radiotherapy to reirradiation was 24(range 13-176) months. Six patients had recurrence in the neck lymph nodes. According to the 2008 Chinese guangzhou Sting System ,The classification distribution at recurrence was 4 for rT2, 11 for rT3, and 16 for rT4; 25 for N0, 4 for N1, 42for N2; 3forⅡ,12 forⅢ,16forⅣ. Before reirradiation using intensity-modulated radiotherapy, Thirty-one patients received 2-3 cycles of induction chemotherapy with TP regimen, cisplatin﹙ DDP﹚ 20mg/m2 on Day 1-4 and Docetaxel(TXT)60mg/m2 on Day 1, Chemotherapy once every three weeks. During the same period for intensity-modulated radiotherapy,two cycles of the TP scheme were achieved. IMRT was given with the sequential tomothempy system (N0MOS Corvus systems)of6 Mv X-rays.Prescription dose was 64-68Gy(median dose:66Gy ) in GTV-T,with the fractional dose of 2.19-2.33 Gy(median fractional dose:2.21Gy ); Prescription dose was 64-66Gy(median dose:65Gy) in GTV-N,Prescription dose was 54-58Gy(median dose:55Gy) in CTV.RESULTSAfter two–three circles of induction chemotherapy, twenty-four patients (77.4%) achieved partial regression of primary tumor, seven(22.6%) had stable disease.Of the six patients with synchronous nodal disease, one(16.7%) had partial regression of neck nodes, five (83.3%)had stable disease. The overall response rate was 77.4% for primary tumor and 16.7% for nodal disease. Overall 22 patients(71%) achieved complete regression after treatment. After concurrent chemoradiotherapy, 20 patients (64.5%) achieved complete regression of primary tumor, 7 (22.6%) had partial regression, and 4(12.9%) had stable disease. Of the six patients with synchronous nodal disease,1(16.7%)had complete regression of neck nodes,3(50%)had partial regression, and 2(33.3%)had stable disease. The overall response rate was 87.1% for primary tumor and (66.7% )for nodal disease. Overall 19 patients (61.3%) achieved complete regression, 6(19.35%)had partial regression, and 6(19.35%)had stable disease, The overall response rate was 80.6% after treatment. After 3 months radiotherapy, 22 patients (71%) achieved complete regression of primary tumor, 7 (22.6%) had partial regression, and 2(6.4%) had stable disease. Of the six patients with synchronous nodal disease,2(33.3%)had complete regression of neck nodes,3(50%)had partial regression, and 1(16.7%)had stable disease. The overall response rate was 93.6% for primary tumor and 83.3% for nodal disease. Overall 21 patients (67.7%) achieved complete regression, 7(22.6%)had partial regression, and 3(9.7%)had stable disease, The overall response rate was90.3%. The results of treatment plan showed that the median volume of GTV-T and GTV-N was37.46cm3(14.30～167.52cm3), 3.26(1.74-6.57cm3) respectively.DVH recealed that the mean dose of covering GTV-T (D95) ,GTV-N(D95)was 65. 56 Gy,62.68Gy respectively and the mean volume of GTV-T (V95),GTV-N(V95) receiving the 95 % dose was 96. 69%,99.56% respectively. The mean dose of GTV-T , GTV-N and CTV in the targets were 71. 2Gy , 68. 02 Gy and 65.4 Gy respectively.mean fractional dose in GTV-T was 2.23 Gy(range 2.19-2.33Gy). In Acute toxicity reaction,the occurrence rates of bone marrow suppression(especially the occurrence rates of grade 3-4 neutropenia)、nauseation、vomit and atrichia,mucositis,were common,but did not effect the treatment.The median follow-up time was 13 months (range 4 to 23months) .1-year local progression-free survial (LPF), nodal progression-free survial(NPF), loco-regional progression-free survial (LRPF), distant metastasis-free survial (DMF), and overall survival(OS) rates were 74.2%,87.1%,67.7%,90.3%,83.9% respectively.during the follow-up, late toxicities Were common,but most Grade 1-2. CONCLUSIONTP scheme induction chemotherapy plus concurrent chemoradiotherapy for locally advanced recurrent NPC is an effective treatment means and recent effect is reliable; acute toxicities are common, but can be tolerated, most patients after symptomatic treatment can complete the treatment as planned. During the follow-up , late radiation reactions are more common. Long-term outcomes and late toxicities need further study and follow-up.