[Abstract] Objective To evaluate the efficacy refuse surgery or surgical contraindications early non-small cell lung cancer patients receiving low split three-dimensional conformal radiation therapy (3DCRT), adverse reactions and complications. Methods 39 patients with histopathological and (or) cytological diagnosis of early-stage non-small cell lung cancer patients refused surgery or surgical contraindications to accept 3DCRT, split dose 4 ~ 6Gy / 5 times / week, total DT 60 ~ 76Gy, relative biological dose to 80.6 ~ 100.4Gy, and and the target area includes only primary tumor and metastatic lymph nodes, 18 cases with 2-4 cycles of chemotherapy. CR rate was 66.7% (26/39), in which the relative biological dose <a 90Gy The CR rate of 50% (9/18), ≥ 90Gy CR rate of 80.9% (17/21), the difference was statistically significant ( P <0.05). The 1 -, 3 -, and 5-year survival rates were 100%, 84.2%, 33.3%, the median survival time was 42 months, slightly lower than the traditional surgical efficacy. Does not appear more than three radiation esophagitis, 4 radiation pneumonitis occurred in only 1 case, the rest are less than 3. Conclusion 3DCRT can replace surgical treatment of early-stage non-small cell lung cancer need to be further carried out a randomized study.

【Key Words】 cancer; non-small cell lung cancer; radiotherapy; surgery; prognosis

Clinical Observation of Hypo  fractionated 3DCRT for Patients with Initial Non  small Cell Lung Cancer

    LONG Zhi  xiong *, LI Yu  xin, ZHU Jiang, CHEN Gui  ming, PENG Yun  wu, YANG Xian  guo

    Department of Oncology, The Second People’s Hospital of Jingmen, Jingmen 448000, China (* Present: The Fifth Hospital of Wuhan) Abstract: Objective To evaluate the therapeutic effect, adverse effect and complications of hypo  fractionated three  dimensional conformal radiotherapy (3DCRT) for patients with initial non  small cell lung cancer (NSCLC). Methods Thirty  nine patients were finally diagnosed by pathohistology and (or) cytology, all the patients who refused to be treated by surgery or couldn’t be treated by surgery received hypo  fractionated 3DCRT, the fractionated doses were from 4Gy to 6Gy, five times a week, the total doses were from 60Gy to 76Gy, the biologically effective doses (BED) were from 80.6Gy to 100.4Gy. The plan targeted volume (PTV) included the primary tumor and metastatic nodes. 18 cases of them were combined with 2 ~ 4 cycles chemotherapy after radiotherapy.Results The complete response (CR) rate was 66.7% (26/39), in which the CR rate of whose BED <90Gy was 50% (9/18), the CR rate of whose BED ≥ 90Gy was 80.9% (17/21), there was significant difference between the patients whose BED <90Gy and whose BED ≥ 90Gy (P <0.05). The overall 1 year, 3 year, 5 year survival rate was 100%, 84.2% and 33.3%, respectively. The therapeutic effects were a little less than the radical resections. The radiation esophagitis higher than grade 3 was not found and only one patient was accompanied with grade 4 radiation pneumonitis. Conclusion Could hypo  fractionated 3DCRT replace operation in the treatment of initial non  small cell lung cancer? It deserves doing research further.

    Key words: Cancer; Non  small cell lung cancer; Radiotherapy; Operation; Prognosis

 Our hospital from March 1998 to December 2006 low split three-dimensional conformal radiotherapy (3DCRT) treatment of inoperable or refuse surgery early non-small cell lung cancer (NSCLC) 39 cases are as follows.

    1 Materials and Methods

    1.1 Clinical data

    Disease can not surgery or refuse surgery early non-small cell lung cancer 39 cases to accept low split three-dimensional fitness shaped radiotherapy, merger have medical disease failed surgery 15 cases, family members or patients refused surgical treatment of 24 cases, including Ⅰ A 17 Li Ⅰ stage B 10 cases, Ⅱ A in 10 cases, Ⅱ B, 2 cases; 29 male and 10 females; ages 58 to 79 years old, with a median age of 67 years; 22 cases of squamous cell carcinoma, adenocarcinoma in 13 cases, two cases of adenosquamous carcinoma, large cell carcinoma in 2 cases; central lung cancer, 21 cases of peripheral lung cancer 18 cases; KPS ≥ 90 marks.

    1.2 Treatment

    Ⅰ A 17 cases of 39 patients using radiotherapy, chemotherapy plus radiotherapy Ⅰ B and Ⅱ 22 cases, 18 patients. Chemotherapy with MVP or NP program, a total of 2 to 4 cycles. Completed 3DCRT radiotherapy, chemotherapy after. All patients treated with radiotherapy using a stereotactic body frame and vacuum cushion to suction vacuum Fixed patients line CT enhanced non-helical slow scan positioning the set surface markers, and each floor 3 ~ 5mm (9 cases 3mm rest 5mm), CT data transmission to the the Star2000 treatment system, select the anchor point, outlined the body surface contour, outline the naked eye or image visible target volume (GTV) target sensitive organs, peripheral lung cancer with lung window, central lung cancer with mediastinal window outline the GTV, three-dimensional reconstruction, based on the target volume, shape, size, position, and relationship with the surrounding structures, based on the the beam directions outlook (BEV) and volume dose histogram (DVH) to determine the angle of the radiation field and treatment programs, and then according to the treatment plan template Figure plexiglass accurate processing to produce conformal block, proven by the multi-leaf collimator in linear accelerator 6MV implementation graded three-dimensional conformal radiotherapy. Expanding outside the planning target volume (PTV) on the basis of the GTV 10 ~ 20mm. Lesions due to respiratory movements can cause up and down movement, so in the processing block conformal external expansion in the Z-axis direction of each of the irradiation field, respectively 20 ~~ 25mm. Tumor ≤ 3cm 3 to 5 non-coplanar arcuate wild treatment 3cm tumor 5 to 7 coplanar conformal fixed irradiation field is selected to adjust the incident angle, to avoid the sensitive organs, the correction dose distribution, so that 90 % ~ 95% isodose line includes PTV, V20 is controlled at 30% or less. Split dose of 4 ~ 6 Gy / 5 times / week, target includes only primary tumor and metastatic lymph nodes, without prophylactic irradiation of mediastinal lymph nodes, radiation dose, according to the the V20 permit given the appropriate dose radiotherapy total DT: 60 ~ 76Gy, median dose of 70Gy (5Gy, 14 times). Translated by L  Q formula (α / β value calculated according to 10), the relative biological dose of 80.6 ~ 100.4Gy, which, <90Gy in 18 cases, ≥ 90Gy 21 cases.

    1.3 Evaluation of treatment side effects

    3DCRT acute toxicity and side effects observed include lung and esophagus. Evaluation criteria in accordance with the RTOG criteria.

    1.4 Follow-up

    Follow-up to January 1, 2007, the follow-up rate of 100%, followed up for at least five years, 18 cases.

    1.5 statistical methods

    The survival rate calculated using the Kaplan  Meier method.

    2 Results

    2.1 near term efficacy

    March review of CT to evaluate the efficacy: CR 26, PR 12, SD 1 case after the end of treatment, PD 0 cases, the response rate (CR + PR) was 97.4% (38/39); <90Gy efficiency of 94.4% (17 0.05)。">/ 18), ≥ 90Gy efficiency of 100% (21/21), the latter a higher efficiency, but the difference was not statistically significant (χ2 = -0.07, P> 0.05). The CR rate was 66.7% (26/39), the relative biological dose <90Gy in 50% (9/18), ≥ 90Gy was 80.9% (17/21). The difference was statistically significant (χ 2 = 4.178, P <0.05). The 1 -, 3 -, and 5-year survival rate was 100% (39/39), 84.2% (32/38), 33.3% (6/18), the median survival time was 42 months. 3 cases (7.69%) during follow-up selective lymph node failure, CR 26 cases, 4 cases of recurrence, residual tumor rate of 33.3% (13/39) recurrence survival rate up to 43.6% (17/39). 12 patients died, six cases of uncontrolled death due to tumor, 6 patients with distant metastases death.

    2.2 toxicity

    3DCRT acute toxicity of a radiation pneumonitis four cases, two cases, 1 case of 4 radiation pneumonitis occurred in patients with chronic bronchitis; V20 <20% without radiation pneumonitis, V20 20% to 25% four cases occurred a radiation pneumonitis, 2 1 V20 25% to 30% of radiation pneumonitis occurred in 1 patient 4. Low split 3DCRT group 2 patients with central lung cancer treatment achieved CR, six months after the occurrence of massive hemoptysis, including one case died. Radiation esophagitis occurred nine cases are three. Minor radiation injury of the blood system, the clinical not seen more than 3 degrees of bone marrow suppression.

    3 Discussion

    The main reason for the failure of conventional radiotherapy local control, radical conventional radiotherapy dose needs to be improved. Bradley et al [1] study the lung the 3DCRT found did not undergo the selective lymphatic drainage district irradiation (ENI) does not affect the treatment effect. Robertson et al [2] conformal radiotherapy incremental research Ⅰ ~ Ⅲ non-small cell lung cancer, prophylactic irradiation the mediastinal area without separate treatment failure. Group 3DCRT not line ENI only three cases (7.67%) during follow-up selective lymph node failure, a lower incidence of regional lymph node recurrence is not the main problem. 3DCRT improve the efficacy of the main ways to narrow the target volume, improve target irradiation dose. Wu KL et al [3] reported 3DCRT treatment Ⅰ Phase II NSCLC dose escalation trial prospective study with dose escalation to 78 Gy of radiation pneumonitis does not appear more than three, the 2-year survival rate of 44%; Belderbors JS, et al [4] reported 3DCRT treatment Ⅰ Ⅱ 40 cases of lung cancer, dose raised to 81Gy, three cases of radiation pneumonitis. Hayman Ⅰ ~ Ⅲ 3DCRT treatment of non-small cell lung cancer, the dose raised to 102.9Gy, toxicity can be tolerated. Hiraoka A retrospective analysis of 13 medical institutions in Japan, 241 patients with early NSCLC low split the results of three-dimensional conformal radiation therapy, the relative biological effective dose (BED) <100Gy BED ≥ 100Gy two groups, the local recurrence rate was 20 % and 6.5%; BED ≥ 100Gy tumor accepted, the 3-year survival of the surgical group and can not tolerate surgery group were 91% and 50% can surgery who can not tolerate surgery is effective.

    4 ~ 6Gy / the group, the total amount of 60 to 76 Gy, the relative biological dose 80.6 ~ 100.4Gy did high dose of radiotherapy dose and biological effects compared to the other author [5  6] CR rate of 66.7%, only 1 case of 4 radiation pneumonitis, 1 -, 3 -, and 5-year survival rate of 100%, 84.2% and 33.3%, slightly lower than the surgery reported efficacy may be related to the radiation resistant to. Forward were higher than those reported in China, may be a result of this study, to refuse surgical cases more, Karnofsky score, generally good, and the biological effects of high doses than those of the other author [5  6]. , 3DCRTCR was 66.7% (26/39), the relative biological dose <90Gy CR rate of 50% (9/18), ≥ 90Gy CR rate of 80.9% (17/21), both the difference was statistically significant (P <0.05 ), residual tumor rate was 33.3% (13/39) CR 26 cases, 4 cases of recurrence, relapse survival rate as high as 43.3% (17/39). Tumor uncontrolled death the 3DCRT group compared with traditional surgery, local control of a direct impact on the 3DCRT treatment of early non-small cell lung cancer, tumors did not control and transfer of death is still 3DCRT the main reason for the failure. V20 permitted tumor dose to be further improved.

    Split time dose, at Kim Ming, etc. [5] reported 60 cases of Ⅰ Phase Ⅱ NSCLC low split accelerated radiotherapy group 4Gy / times, 5 times / week, total dose of 48 Gy, conventional split group 2Gy radiation. / Times, 5 times / week, total dose 66Gy, low-radiotherapy group 1 -, 2 – and 3-year survival rates were 80%, 65% and 60% of conventional fractionated radiotherapy group were 60%, 45% and 33.3%, median survival was 27 months and In 19 months, the low-radiotherapy group better. Slotman [7] accelerated radiotherapy (48Gy/12 low split) in patients with stage I NSCLC, 2,4-year survival rates were 93% and 76%, the recurrence rate was only 19%, to analyze the reasons may be shortened for low-radiotherapy treatment time, reduce tumor cell accelerated repopulation opportunities. The group with the dose of the 4 ~ 6Gy graded, 5 times a week, throughout the course of 2 to 3 weeks to end, shorten the course of treatment, in part to overcome the tumor cells to accelerate the negative impact of repopulation and sublethal damage repair , thereby increasing the rate of tumor control. Central lung distance vascular, bronchial, esophageal late response organizations, low split radiotherapy as early as late reaction greater than the biological effects of tumor response organizations, to reduce split dose is recommended in order to reduce late radiation reaction; peripheral lung cancer away from the The organization divided doses and total dose may be appropriate to increase the radiation-induced lung injury compared with surgical resection of lung injury within a certain range.

    Graham et al [8] found that the the V20 size of not only related to the incidence of radiation pneumonitis, and is closely related to the severity of radiation pneumonitis. The lung is a “parallel organization", part of the functional units of the destruction of the other functional units and will not damage. In this study, the lungs seen as an organ, the V20 control in 30%, only 1 case of a history of poor lung disease lung function in patients with 4 radiation pneumonitis, similar to the results reported in the literature. V20 <30%, to a certain range in divided doses (<10Gy / time) equally well in the case of one of the indicators of control radiation pneumonitis, and can still be as low fractionated radiotherapy. Closely related to the occurrence of radiation pneumonitis and pulmonary exposed volume and dose, with each divided doses, is not very different in the case of low-dose, single dose may 3DCRT group, although the increase but little over 2Gy lung volume, it is not cause lung damage increased significantly. Careful analysis found that 50% of the dose interval preventive treatment, the median dose 5Gy 14, the group the PTV GTV outside the 10 ~ 20mm Anthropometric range of movement of its radiation dose distribution outside the PTV 20 ~ 30mm just subclinical lesions regional, this area is just 50% dose line wrapping, approximately equivalent to a dose of 2.5Gy 14, exactly the required dose of subclinical lesions, subclinical lesions may play a preventive role, 30 percent to 50 % dose line interval is small, the 30% dose line range V20 regional V20 <30%, its graded about 1.5Gy, less than the conventional fractionated points times the amount of low split 3DCRT control subclinical lesions and subclinical lesions outside dose compared with conventional radiotherapy decreased in the same biological effect dose case, better protection of normal lung tissue.

    3DCRT treatment of early-stage non-small cell lung cancer 1 -, 3 -, and 5-year survival rate in this group were 100%, 84.2%, 33.3%, and 1, 3, 5-year survival rate than traditional surgery is slightly lower. 3DCRT as refuse surgery or surgical contraindications early the treatment of choice in patients with non-small cell lung cancer, can replace the surgical treatment of early-stage non-small cell lung cancer needs further randomized studies.