Ⅰ期子宫内膜癌术后放疗的临床分析

目的 回顾分析265例Ⅰ期子宫内膜癌术后放疗疗效和不良反应。方法 1999—2012年进行术后放疗的Ⅰ期子宫内膜癌患者共265例。病理类型为子宫内膜样腺癌占85.3%(226例)。根据FIGO2009手术—病理分期。术后辅助放疗方式包括盆腔外照射35例(13.2%)、单纯阴道内照射107例(40.4%)和内外照射联合治疗123例(46.4%)。Kaplan-Meier法计算生存率并Logrank检验差异,Cox模型进行预后因素分析。结果 5年随访率为85.7%。5年OS、PFS、局部复发、远处转移率分别为92.8%、89.7%、4.5%、6.4%。发生3级急性放射性肠炎者仅1例(0.4%),3、4级骨髓抑制者分别为4例(1.5%)、1例(0.4%),1例(0.4%)出现3级慢性肠炎。多因素分析显示子宫下段受累是影响OS和PFS的预后因素(P=0.041、0.001),放疗前贫血是影响OS的因素(P=0.048)。 结论 子宫内膜样腺癌为主的Ⅰ期内膜癌患者进行术后辅助放疗的疗效良好,不良反应轻微,放疗前贫血和子宫下段受累是影响OS的重要因素。     

Adjuvant hormonal therapy for stage I endometrial cancer

Question

What is the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer?

Perspectives

There is little consensus on the role of adjuvant treatment for patients with stage i endometrial cancer. Although the use of hormonal therapy has been established in advanced disease, less agreement has emerged concerning the benefits of adjuvant hormonal therapy for patients with early-stage disease. The objective of the present evidence series was to review the existing literature on the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer.

Outcomes

Reports were sought that included at least one of the following outcomes: overall survival, disease-free survival, recurrence (local, or distant, or both), adverse effects, and quality of life. Because of the potential for long-term adverse effects with adjuvant hormonal treatment in this patient population, especially with regard to thromboembolic or cardiovascular events, the rates of non-cancer-related death were also of interest.

Methodology

The medline, embase, and Cochrane Library databases were systematically searched for randomized controlled trials, practice guidelines, systematic reviews, and meta-analyses. The resulting evidence informed the development of the clinical practice guideline. The systematic review with meta-analyses and practice guideline were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (dsg).

Results

Nine randomized trials and one published meta-analysis comparing adjuvant hormonal therapy with no adjuvant therapy in women with stage i endometrial cancer constituted the evidence base. One trial reported a statistically significant survival benefit with adjuvant progestogen as compared with no further treatment (97% vs. 69%, p < 0.001). In that trial, the treatment group had a higher number of patients with less myometrial invasion, and a lower number of patients with advanced-stage disease. These differences in baseline characteristics between the randomized groups were considered to be clinically important. In addition, the results of that trial were not consistent with those of other trials, and the trial was a source of statistical heterogeneity when data were pooled across trials.In two of the nine randomized trials, statistically significant recurrence-free benefits were detected with adjuvant hormonal therapy as compared with no further therapy. In one trial, the difference between the rates of recurrence was 16%; however, the methodologic concerns related to that that trial limited its relevance. In the other trial, the difference between the rates of recurrence was 5%. In that trial, patients were at a high risk of recurrence. None of the remaining seven randomized trials reported any significant difference in recurrence rates between treatment groups.The meta-analysis identified in the literature detected no statistically significant recurrence-free or overall survival benefit associated with adjuvant hormonal therapy as compared with no adjuvant therapy [odds ratio (or): 1.05; 95% confidence interval (ci): 0.88 to 1.24). Those results are consistent with the results of the meta-analysis in the present report, which included an additional two trials (or: 1.10; 95% ci: 0.91 to 1.34).

Practice Guideline

Target Population

This clinical recommendation applies to women with newly diagnosed stage i endometrial cancer.

Recommendation

The available evidence does not demonstrate any benefit for adjuvant hormonal therapy. The use of hormonal therapy is not recommended as adjuvant treatment for patients with stage i endometrial cancer.     

Clinical evidence on PET-CT for radiation therapy planning in cervix and endometrial cancers

PET-CT plays an increasing role in the diagnosis and treatment of gynaecological cancers. In cervix cancer, whilst MRI remains the best imaging technique for initial primary tumor staging, PET-CT has been showed to be a highly sensitive method to determine lymph node status, except in patients with early-stage cervical cancer where PET-CT cannot replace surgical exploration of pelvic lymph nodes. In patients with advanced cervical cancer, PET-CT has the potential of showing lymph node metastasis not only within the pelvis, but also outside the pelvis, more particularly in the para-aortic area. PET-CT has also been described as a useful tool in 3-D-based adaptative brachytherapy. In endometrial cancer, the issues are different, as the recent decade has seen a therapeutic decrease in early-stage disease, especially in postoperative radiation therapy, whilst more advanced disease have been approached with more aggressive treatments, integrating chemotherapy and external beam radiotherapy. Lymph node status is also an important issue and PET-Scan may replace lymph node surgical procedure particularly in obese patients.     

Adjuvant external beam therapy for pathologic stage I and occult stage II endometrial carcinoma

Eighty-six patients with pathologic Stage I or occult Stage II carcinoma of the endometrium and myometrial invasion and/or Grade 2 or Grade 3 histologic condition received whole-pelvis external radiation therapy (RT) after extrafascial total abdominal hysterectomy and bilateral salpingo-oophorectomy. Twenty-one patients received 4250 cGy in 25 daily fractions for 5 weeks (Group 1), 28 received 4500 cGy in 25 daily fractions for 5 weeks (Group 2), and 37 received 5100 cGy in 30 daily fractions for 6 weeks (Group 3). Seventeen patients had intravaginal brachytherapy after whole-pelvis RT. Local recurrence developed in two patients (2.3%) (one in Group 1 and one in Group 2). Statistical analysis showed that the depth of myometrial invasion significantly influenced survival (P = 0.016). Tumor grade, pathologic stage, whole-pelvis radiation dose, and the use of brachytherapy did not influence survival. Complications occurred in 9.5% of patients in Group 1, 24.7% in Group 2, and 40.5% in Group 3. Three patients who received brachytherapy had rectal injuries. The authors conclude that 4250 cGy in 25 fractions for 5 weeks of whole-pelvis RT appears to induce fewer complications than higher doses, and may be sufficient to prevent local recurrence in most patients who require adjuvant RT. A clinical trial is needed to determine the optimum dose-time-fractionation regimen.     

Value of routine follow-up procedures for patients with stage I/II cervical cancer treated with combined surgery-radiation therapy.

BACKGROUND: The aim of this study was to determine the value of routine follow-up for the detection of recurrence in patients treated for cervical cancer. PATIENTS AND METHODS: From 1986 to 1998, 583 women with stage I and II cervical carcinoma were treated with combined surgery-radiation therapy. After treatment, follow-up was based on clinical examination, a systematic Pap smear and radiography (chest X-ray and abdomino-pelvic ultrasonography). RESULTS: Forty-five patients had recurrence observed with a delay > or = 6 months following the end of treatment. Thirty-eight patients had symptoms and seven were asymptomatic at the time of their recurrence. Among asymptomatic patients only two recurrences were diagnosed following routine examinations. Survival is similar in asymptomatic and symptomatic recurrent patients. CONCLUSIONS: In conclusion, follow-up of patients treated for cervical cancer based on routine Pap smears and systematic radiography does not permit earlier detection of recurrence and does not increase survival.     

Surgery and postoperative radiation therapy in stage II endometrial carcinoma.

The traditional approach to patients with stage II endometrial carcinoma is preoperative radiation therapy (RT) followed by surgery. Currently, many patients are treated with primary surgery and postoperative RT. We retrospectively reviewed the outcome of 44 stage II (32 IIA, 12 IIB) patients who underwent surgery and postoperative RT. Nine (20%) had microscopic cervical involvement noted before surgery, and 35 (80%) had occult involvement noted postoperatively. Postoperative RT consisted of whole pelvic RT (WPRT) (50%), vaginal brachytherapy (VB) (18%), or both (32%). At a median follow-up of 40 months, the 5-year actuarial disease-free survival was 72.4%. Two patients (4%) had recurrence in the pelvis (one vagina, one lateral pelvis). Eighteen stage IIA patients treated with WPRT alone and eight stage IIA patients, without deep myometrial invasion (MI), were treated with VB alone, and remained controlled in the pelvis. Extrapelvic recurrences occurred in 12 patients (25%), primarily in those with deep MI and/or grade 2-3 disease. Our results suggest that patients with stage II endometrial carcinoma with microscopic or occult cervical involvement treated with surgery and postoperative RT have a favorable outcome. A high rate of pelvic control is achieved with RT tailored to the pathologic findings.     

Promising clinical outcome of stereotactic body radiation therapy for patients with inoperable Stage I/II non-small-cell lung cancer

PURPOSE: To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy in patients with Stage I/II non-small-cell lung cancer. METHODS AND MATERIALS: Forty-three patients with inoperable Stage I/II non-small-cell lung cancer underwent treatment prospectively using the stereotactic gamma-ray whole-body therapeutic system (body gamma-knife radiosurgery) with 30 rotary conical-surface Co(60) sources focused on the target volume. Low-speed computed tomography simulation was conducted, which was followed by three-dimensional conformal radiotherapy planning. A total dose of 50 Gy was delivered at 5 Gy/fraction to the 50% isodose line covering the planning target volume, whereas a total dose of 70 Gy was delivered at 7 Gy/fraction to the gross target volume. The median follow-up duration was 27 months. RESULTS: Three to 6 months after treatment, the complete response rate for body-gamma knife radiosurgery was 63%, and the overall response rate was 95%. The 1-year, 2-year, and 3-year local control rates were all 95% in all patients. The 1-year, 2-year, and 3-year overall survival rates were 100%, 91%, and 91%, respectively, in patients with Stage I disease and 73%, 64%, and 64%, respectively, in those with Stage II disease. Only 2.3% (1/43) of the patients had Grade 3 pneumonitis. CONCLUSION: Our highly focused stereotactic body radiotherapy method resulted in promising local control and survival with minimal toxicity.     

Aspirin improves outcome in high risk prostate cancer patients treated with radiation therapy

Purpose High-risk prostate cancer (PC) has poor outcomes due to therapeutic resistance to conventional treatments, which include prostatectomy, radiation, and hormone therapy. Previous studies suggest that anticoagulant (AC) use may improve treatment outcomes in PC patients. We hypothesized that AC therapy confers a freedom from biochemical failure (FFBF) and overall survival (OS) benefit when administered with radiotherapy in patients with high-risk PC.Materials and Methods Analysis was performed on 74 high-risk PC patients who were treated with radiotherapy from 2005 to 2008 at UT Southwestern. Of these patients, 43 were on AC including aspirin (95.6%), clopidogrel (17.8%), warfarin (20%), and multiple ACs (31.1%). Associations between AC use and FFBF, OS, distant metastasis, and toxicity were analyzed.Results Median follow-up was 56.6 mo for all patients. For patients taking any AC compared with no AC, there was improved FFBF at 5 years of 80% vs. 62% (P = 0.003), and for aspirin the FFBF was 84% vs. 65% (P = 0.008). Aspirin use was also associated with reduced rates of distant metastases at 5 years (12.2% vs. 26.7%, P = 0.039). On subset analysis of patients with Gleason score (GS) 9–10 histology, aspirin resulted in improved 5-year OS (88% vs. 37%, P = 0.032), which remained significant on multivariable analysis (P &lt; 0.05).Conclusions AC use was associated with a FFBF benefit in high-risk PC which translated into an OS benefit in the highest risk PC patients with GS 9–10, who are most likely to experience mortality from PC. This hypothesis-generating result suggests AC use may represent an opportunity to augment current therapy.     

The number of high-risk factors is related to outcome in stage II colonic cancer patients

Background

A subgroup of stage II colonic cancer patients are considered to be at high-risk for recurrent/metastatic disease based on 1) tumour obstruction/perforation 2) <10 lymph nodes 3) T4 lesions and 4) lymphangio-invasion. Their prognosis is regarded as comparable to stage III (T1-4N+M0) colonic cancer and it is therefore strongly advised to treat them with adjuvant chemotherapy. The purpose of this study was i) to determine the magnitude of prognostic significance of the conventional high-risk factors and ii) to determine whether the number of high-risk factors influences outcome.

Methods

We retrospectively analyzed 212 stage II colonic cancer patients undergoing surgery between January 2002 and December 2008. No adjuvant chemotherapy was given. Survival analyses were performed.

Results

154/212 (73%) patients were considered to be high-risk patients based on conventional high-risk factors. 58 patients did not meet any high-risk factor, 125 patients met 1 high-risk factor and 29 patients met ≥2 high-risk factors. Median follow up was 40 months.Multivariate analysis identified four independent risk factors for recurrent/metastatic disease: age, obstruction, perforation and lymphangio-invasion.The three-year-DFS-rates for the low-risk group, the high-risk group with 1 high-risk factor and the high-risk group with ≥2 high-risk criteria are 90.4%, 87.6% and 75.9% respectively.Patients meeting ≥2 conventional high-risk criteria had a significantly worse three-year disease free survival (p < 0.002).

Conclusions

Four independent high-risk factors were identified. The number of high-risk factors does influence outcome. More attention should be given to the definition and treatment of high-risk stage II colonic cancer patients.     

Poorer outcome in Polynesian patients with prostate cancer treated with definitive conformational radiation therapy

Purpose

To compare freedom from biochemical failure (FFBF) of French Polynesian (FP) and Native European (NE) prostate cancer patients after definitive conformal radiotherapy (RT).

Patients and methods

Data were reviewed from medical records of 152 consecutive patients (46 FP and 106 NE) with clinically localised prostate cancer treated with definitive RT. Neoadjuvant androgen deprivation therapy (ADT) was used in 22% of cases. Definition for biochemical failure was a rise by 2 ng/mL or more above the nadir prostate-specific antigen (PSA) level. The median follow-up was 34 months.

Results

In comparison to NE patients, FP patients were younger (p = 0.002) with a higher low-risk proportion (p = 0.06). Probability of 5-year FFBF was 77% in the NE cohort and 58.0% in the FP cohort (p = 0.017). Univariate analysis showed that FP ethnicity was associated with worse prognosis in high-risk tumours (p = 0.004). Cox multivariate analysis showed that factors associated with FFBF were risk category (p < 0.017), and FP origin (p = 0.03), independently of ADT and radiation dose.

Conclusion

FP ethnicity was an independent prognostic factor for biochemical relapse after definitive conformal RT for prostate cancer.     

Extended mantle radiation therapy for pathologic stage I and II Hodgkin's disease

Between 1968 and 1983, 135 patients with pathologic stage (PS) I and II Hodgkin's disease were treated with extended mantle radiation technique (EMRT) at Michael Reese Hospital and the University of Chicago Center for Radiation Therapy. EMRT combines both standard mantle and para-aorta fields (M-PA) in one port. Actuarial disease-free survival at 5 and 10 years was 82.5%. Actuarial overall survival was 96% and 83% at 5 and 10 years, respectively. Acute complications were evaluated in 112 patients available for analysis. Severe nausea and vomiting occurred in 13%, weight loss of greater than 10% of body weight in 19%, and acute hematologic toxicity in 4% of patients. Bone marrow suppression was transient and did not interfere with subsequent delivery of salvage treatment with either chemotherapy or radiation therapy in 22 patients who relapsed. The cost of EMRT is 40% lower than the cost of treatment with M-PA. The median treatment time was 38 days, 33% less than the 56 days for M-PA field assuming no interruptions. These results suggest that the EMT is a safe and effective treatment tolerated by most patients. The advantages of this method are eliminating the possibility of technical error of matching between mantle and para-aortic field, decreasing overall treatment time, and reducing the cost.     

Impact of treatment interruptions due to toxicity on outcome of patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone

We investigated the effect of treatment interruptions due to high-grade (3) toxicity on outcome of patients with early stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy (Hfx RT). Of 116 patients treated with total tumour doses of 69.6 Gy, 1.2 Gy b.i.d. fractionation, 44 patients refused surgery while 72 patients were medically inoperable due to existing co-morbid states. Patients who were medically inoperable had worse KPS (P=0.0059) and more pronounced weight loss (P=0.0005). Among them, 12 patients experienced high-grade toxicity and 11 of them with either acute (n=6) or ‘consequential’ late (n=5) high-grade toxicity requested interruption in the Hfx RT course (range, 12–25 days; median, 17 days). Superior survival (OS) was observed in patients who refused surgery when compared to those who were medically inoperable (P=0.0041), as well as superior local recurrence-free survival (LRFS) (P=0.011), but not different distant metastasis-free survival (P=0.14). Cause-specific survival (CSS) also favoured patients who refused surgery (P=0.004). Multivariate analysis showed independent influence of the reason for not undergoing surgery on OS (P=0.035), but not on LRFS (P=0.084) or CSS (P=0.068). Patients who refused surgery did not experience high-grade toxicity (0/44), whereas 11 of 72 patients with medical inoperability and co-morbid states experienced high-grade toxicity and had treatment interruptions to manage toxicity (P=0.0064). Patients without treatment interruptions had significantly better OS (P=0.00000), LRFS (P=0.00000) and CSS (P=0.00000) than those with treatment interruptions. When corrected for treatment interruptions, the reason for not undergoing surgery independently influenced OS (P=0.040), but not LRFS (P=0.092) or CSS (P=0.068). In contrast to this, treatment interruption was independent prognosticator of all three endpoints used (P=0.00031, P=0.0075 and P=0.00033, respectively). When 11 patients with treatment interruptions were excluded, the reason for not undergoing surgery still affected OS (P=0.037) and CSS (P=0.039) but not LRFS (P=0.11). Multivariate analyses using OS, CSS and LRFS showed that the reason for not undergoing surgery affected OS (P=0.0436), but neither CSS (P=0.083) nor LRFS (P=0.080).     

Preoperative or postoperative brachytherapy for patients with endometrial carcinoma stage I and II

In endometrial carcinoma, vaginal vault brachytherapy is performed to improve the local control rate and to decrease vaginal recurrences. To assess the best chronology of this brachytherapy compared to surgery, we have retrospectively analyzed results of treatment of patients treated either with preoperative brachytherapy (60 Gy) and then radical hysterectomy with bilateral salpingo oophorectomy (RH-BSO) (Group 1), or with RH-BSO and then postoperative brachytherapy (60 Gy) (Group 2). There were one hundred twenty-one patients in Group 1 and 63 in Group 2. The mean age was 61.8 years in Group 1 and 64.3 in Group 2. In Group 1, 73% of the patients were Stage I, and 77.6% were in Group 2. The two groups were comparable for histological grading and depth of tumoral invasion into the myometrium. Brachytherapy was delivered with one uterine and two vaginal sources in Group 1 and with three vaginal sources in Group 2. Doses to the reference volume and to reference points were calculated according to ICRU recommendations. Brachytherapy data were similar in the two groups except reference volume, which was smaller in Group 2. Local control rate was 87% in Group 1 and 91% in Group 2. Distant metastasis occurred in 12% of patients in Group 1 and 9% in Group 2. The 5-year actuarial survival rate was 84% in Group 1 and 89% in Group 2. Regarding stage, histological grading, and depth of tumoral invasion, no differences were observed between the two therapeutic groups. The only prognostic factor in the entire population was Stage. The 5-year actuarial survival rate was 91% for Stage I patients and 69% for Stage II (p value less than 0.03). The late severe complication rate was 14% in Group 1 and 7.9% in Group 2, a difference which was not statistically significant. We concluded that since no differences were observed between the two techniques, vaginal brachytherapy should be performed postoperatively when surgery is the first treatment (Stage I or II, grade 1 or 2, and no deep tumoral invasion into the myometrium).     

Breast edema in patients treated conservatively for stage I and II breast cancer

Breast edema was evaluated in 45 patients with Stage I or II breast cancer (including two with simultaneous, bilateral disease), who were treated by breast-preserving treatment approaches. Multiple variable statistical analysis revealed that bra cup size was the only factor significantly related to the appearance of breast edema. Breast edema occurred in 3 of 20 breasts (15%) with bra cup size A or B, as compared to 13 of 27 breasts (48%) with bra cup size C, D or DD(p less than 0.03). Breast edema was more likely to occur in patients who underwent full axillary dissection as compared to those who underwent axillary sampling or no axillary surgery. This observation, however, was not statistically significant. Neither the radiation therapy parameters nor the use of adjuvant chemotherapy were found to be related to the development of breast edema. Breast edema appears to be a transient phenomenon observed most frequently in the first year after the end of irradiation. It was observed much less frequently in those patients evaluated over 1 year following the end of radiation therapy.     

The impact of lymph vascular space invasion on recurrence and survival in patients with early stage endometrial cancer

The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log‐rank test and Kaplan–Meyer methods were used for time‐to‐event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty‐nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P < 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement.