早期宫颈癌术后辅助治疗的研究进展

早期宫颈癌的治疗首选根治性手术,术后存在危险因素的患者需给予放化疗。目前宫颈癌辅助治疗主要依据NCCN推荐的宫颈癌治疗指南,术后存在任何一项高危因素（淋巴结转移、阴道切缘阳性和宫旁浸润）,推荐给予含顺铂同步放化疗;而对于无高危因素,但存在中危因素、符合Sedlis标准的宫颈癌患者,建议术后补充盆腔外照射±含顺铂同期化疗。但是目前早期宫颈癌术后危险因素的评估、辅助治疗的指征以及方式仍存在争议,本文重点阐述早期宫颈癌术后存在危险因素患者辅助治疗的研究进展。     

Evaluation of adjuvant vaginal vault brachytherapy in early stage cervical cancer patients

PurposeAdjuvant external beam radiotherapy (EBRT) was shown to decrease pelvic relapses in patients with an early stage cervical cancer and intermediate-risk histopathological prognostic factors, at the cost of increased bowel morbidity. We examined the feasibility and results of adjuvant brachytherapy alone as an alternative to EBRT in this situation.Patients and methodsMedical records of consecutive patients receiving adjuvant brachytherapy between 1991 and 2018 for an early stage cervical cancer were examined. Patients were included if they presented a pT1a2N0 or pT1b1N0 disease following radical colpohysterectomy. Adjuvant vaginal wall brachytherapy (without EBRT) was indicated because of a tumor size ≥ 2 cm and/or presence of lymphovascular space invasion (LVSI). Patients received 60 Gy to 5 mm of the vaginal wall, through low-dose or pulse-dose rate technique. Patients’ outcome was examined for disease control, toxicities and prognostic factors.ResultsA total of 40 patients were included. Eight patients (20%) had LVSI, 26 patients (65%) had a tumor size ≥ 2 cm. With median follow-up time of 42.0 months, 90% of patients were in complete remission and four patients (10%) experienced tumor relapse, all in the peritoneal cavity, and associated with synchronous pelvic lymph node failure in 2/4 patients. No vaginal or isolated pelvic nodal failure was reported. At 5 year, overall survival was 83.6% (CI95%: 67.8–100%) and disease-free survival was 85.1% (CI95%: 72.6–99.9%). In univariate analysis, probability of relapse correlated with tumor size ≥ 3 cm (P = 0.004). No acute or late toxicity grade more than 2 was reported.ConclusionBrachytherapy alone was a well-tolerated adjuvant treatment for selected patients with intermediate risk factors. The risk of relapse in patients with tumor size ≥ 3 cm was however high, suggesting that EBRT is more appropriate in this situation.     

Histopathologic score predicts recurrence free survival after radical surgery in patients with stage IA2-IB1-2 cervical carcinoma

BACKGROUND: The authors evaluated clinical and pathologic factors that predicted for recurrence after patients underwent radical surgery for International Federation of Gynecology and Obstetrics (FIGO) Stage IA(2)-IB(1-2) cervical carcinoma and developed a simple method of scoring those predictive factors to quantify outcome. METHODS: An analysis was conducted of a prospective radical surgery cervical carcinoma data base. A Cox proportional hazards regression analysis was done for each of the individual factors to estimate individual risk ratios using all available data for each factor. Stepwise and best-model options were used to identify the best combinations as predictors and to calculate adjusted risk ratios. Based on the information obtained, each patient was assigned a categorical score to predict recurrence. The variables used for the score were dichotomized. The differences between the scores in time to recurrence were evaluated using the log-rank test to compare the time to recurrence curves that were generated with the Kaplan-Meier method. RESULTS: Eight hundred seventy-one patients were included in the study, and 66 patients who developed recurrent disease after a median follow-up of 49 months. Tumor size, maximum depth of invasion, pelvic lymph node status, tumor grade, and capillary lymphatic space (CLS) were single predictors for recurrence, and the score, which was based on combinations of these factors, predicted the disease free survival. Maximum depth of invasion, pelvic lymph node status, and CLS were the best combined predictors for recurrence, and they were used to form a second, precise scoring system to predict disease free survival (P < 0.0001; log-rank test). CONCLUSIONS: The scoring system based on maximal depth of invasion, CLS, and pelvic lymph node metastases identified four strata of patients with distinct recurrence free survival. The incremental presence of each factor decreased recurrence free survival after patients underwent radical surgery. Patients with the presence of all three factors had a 5-year recurrence free survival rate of 65%. These patients would be suitable for studies of postoperative adjuvant therapy to improve outcome.     

Adjuvant therapy for high-risk, early stage cervical cancer

The identification of various pathologic risk factors after primary surgical management of early stage cervical cancer portends a higher rate of relapse and decreased survival. Historical attempts to improve outcome focused mainly on the use of adjuvant pelvic radiation, with limited success overall. Analysis of patterns of failure after radical hysterectomy led to better stratification of patients into risk groups and incorporated testing of systemic agents in those considered at high risk of distant failure. Two recently reported randomized, clinical trials have greatly advanced our understanding of the role of postoperative therapy in cervix cancer. In patients with positive nodes, the use of combined adjuvant chemotherapy and radiation significantly improves relapse-free survival and overall survival, compared with radiation alone. For node-negative patients with other primary tumor risk features, pelvic radiation significantly improves relapse-free survival, compared with no further therapy. An observed improvement in survival for irradiated patients awaits statistical confirmation after maturation of the data. Further improvements in adjuvant therapy for high risk, early stage cervical cancer will come from enhanced definition of prognostic variables, better patient selection, and refinements in both local and systemic therapies.     

Aromatase inhibitors as adjuvant therapy for postmenopausal patients with early stage breast cancer

Endocrine therapy of hormone receptor-positive breast tumors is widely used as palliative therapy for metastatic breast cancer and as adjuvant therapy for early stage breast cancer. Tamoxifen has been the definitive standard of hormonal therapies for the last 30 years because of its documented efficacy and reasonable safety profile. Based on encouraging results from trials utilizing the selective, third generation aromatase inhibitors (AIs) in metastatic breast cancer, a number of trials were designed to examine these agents as adjuvant therapies. Trials directly comparing AIs with tamoxifen have, to date, demonstrated superior disease-free-survival with AIs. Likewise, trials examining the use of AIs after tamoxifen have demonstrated better outcomes compared with tamoxifen alone. Additionally, letrozole has been demonstrated to result in superior disease-free-survival after 5 years of adjuvant tamoxifen, compared with no further therapy. In general, the AIs are tolerated at least as well as tamoxifen but decrease bone mineral density and increase osteoporosis due to their lack of estrogenic effects on bone. Based on the fact that AIs appear more effective at preventing contralateral breast cancers than tamoxifen, they are being examined as breast cancer preventives. Despite available data using the AIs as adjuvant therapies, many questions remain unanswered, and further trials will be needed to address these important issues.     

Treatment of depressive symptoms in patients with early stage breast cancer undergoing adjuvant therapy

Background Studies have shown that there is a high prevalence of depression in cancer patients. Women with breast cancer may have an even higher risk of depression particularly in a postmenopausal or estrogen deficiency state. A small number of randomized controlled trials have examined the efficacy of antidepressants compared to that of a placebo in cancer patients, but some results have been difficult to interpret due to a heterogeneous patient group. In the current investigation, we screened newly diagnosed early stage breast cancer patients for depressive symptoms prior to the initiation of adjuvant therapy and investigated whether the oral antidepressant fluoxetine affected depressive symptoms, completion of adjuvant treatment, and quality of life. Methods Patients with newly diagnosed early stage breast cancer were screened for depressive symptoms prior to the initiation of adjuvant therapy. Patients with depressive symptoms were randomized to a daily oral fluoxetine or a placebo. Patients were then followed for 6 months and evaluated for quality of life, completion of adjuvant treatment, and depressive symptoms. Results A high percentage of patients with newly diagnosed early stage breast cancer were found to have depressive symptoms prior to the initiation of adjuvant therapy. The use of fluoxetine for 6 months resulted in an improvement in quality of life, a higher completion of adjuvant treatment (chemotherapy, hormonal therapy, chemotherapy plus hormonal therapy), and a reduction in depressive symptoms compared to patients who received placebo. Conclusions An antidepressant should be considered for early stage breast cancer patients with depressive symptoms who are receiving adjuvant treatment.     

Radical hysterectomy and tailored postoperative radiation therapy in the management of bulky stage 1B cervical cancer

Ninety-two patients with Stage IB cervical cancers having a diameter equal to or greater than 4.0 cm were treated with radical surgery. Thirty-two patients received postoperative radiotherapy because of operative findings suggestive of high risk of pelvic recurrence. All 32 irradiated patients were treated with a standard pelvic field. Four patients also received paraaortic radiotherapy, and ten received intravaginal brachytherapy. Postoperative complications were seen in five patients (two nonirradiated, three irradiated). Projected 5-year survival is 79% (71% 5-year survival in irradiated patients, and 83% 5-year survival in nonirradiated patients). Preoperative evaluation of tumor volume was not found to reliably predict histologic high risk factors such as depth of stromal invasion, risk of lymph node metastases, or presence of extracervical/uterine involvement. A primary surgical approach in this group of patients with large-diameter Stage IB cervical cancers allows definition of those patients who might benefit from a combined surgical and radiotherapeutic approach to treatment based on findings at operation.     

Pilot trial of paclitaxel-trastuzumab adjuvant therapy for early stage breast cancer: a trial of the ECOG-ACRIN cancer research group (E2198)

Background:

Blockade of human epidermal growth factor receptor type 2 (HER2) has dramatically improved outcome for patients with HER2-positive breast cancer. Trastuzumab, an anti-HER2 monoclonal antibody, has previously demonstrated improvement in overall survival (OS) in patients with metastatic and early stage HER2-positive breast cancer. However, trastuzumab can cause congestive heart failure (CHF) with an increased frequency for patients who have also received an anthracycline. The current trial was designed to evaluate the impact of the duration of trastuzumab on CHF.

Methods:

E2198 included 227 eligible women with histologically confirmed stage II or IIIA HER2-positive breast cancer. The patients were randomised to receive 12 weeks of paclitaxel and trastuzumab followed by four cycles of doxorubicin and cyclophosphamide (abbreviated Arm) or the aforementioned treatment with additional 1 year of trastuzumab (conventional Arm). The primary end point was to evaluate the safety of this variable duration of trastuzumab therapy, particularly cardiac toxicity defined as CHF or left ventricular ejection fraction decrease >10%. Secondary end points included disease-free survival (DFS) and OS.

Results:

Compared with 12-week treatment with trastuzumab, 1 year of trastuzumab-based therapy did not increase the frequency or severity of cardiac toxicity: three patients on the abbreviated Arm and four on the conventional Arm experienced CHF. The 5-year DFS was 76% and 73% for the abbreviated and conventional Arms, respectively, with a hazard ratio (HR) of 1.3 (95% CI: 0.8–2.1; P=0.3). There was also no statistically significance difference in OS (HR, 1.4; P=0.3).

Conclusions:

Compared with 12 weeks of treatment, 1 year of treatment with trastuzumab did not significantly increase the risk of cardiac toxicity. Although not powered for efficacy comparisons, the longer duration of trastuzumab therapy did not demonstrate a signal for marked superiority.     

Addition of bevacizumab to three docetaxel regimens as adjuvant therapy for early stage breast cancer

Docetaxel-containing chemotherapy improves disease-free survival (DFS) and overall survival in patients with early stage breast cancer. Bevacizumab improves response rate and DFS in metastatic breast cancer. However, adding antivascular endothelial growth factor therapy to anthracycline-containing chemotherapy may increase cardiotoxicity. This trial evaluates the feasibility of adding bevacizumab to three standard adjuvant docetaxel regimens with a primary endpoint of grade ≥3 congestive heart failure (CHF). Phase IIb, randomized, non-comparative study of women with previously untreated node-positive or high-risk node-negative breast cancer. Human epidermal growth factor receptor 2 (HER2)-negative patients were randomized to: (arm A) doxorubicin + cyclophosphamide followed by docetaxel or (arm B) docetaxel + doxorubicin + cyclophosphamide. HER2-positive patients (arm C) received docetaxel + carboplatin + trastuzumab for 52 weeks. All patients received bevacizumab beginning on day 1 for 52 weeks. Safety data in 212 women (mean age = 53.1 years) show that 1 patient each in arm A (1.3 %) and arm C (1.7 %), and 3 patients in arm B (4.0 %) experienced clinical CHF grade ≥3. A decreased ejection fraction was observed in 1 patient each in arms A and C, and cardiac disorder was observed in 12.8, 22.7, and 8.5 % in arms A, B, and C, respectively. A grade 3/4 treatment-emergent adverse event was reported in 82.1, 84.0, and 52.5 % of participants in arms A, B, and C, respectively. Kaplan–Meier estimates of DFS show rates at 24 months of 85.5, 90.4, and 90.4 % in arms A, B, and C, respectively. Adding bevacizumab to three standard docetaxel-based chemotherapy regimens as adjuvant treatment in patients with node-positive and high-risk node-negative breast cancer resulted in a low rate of clinical CHF grade ≥3. Maintenance bevacizumab monotherapy did not identify any new safety signals. Breast cancer recurrence/relapse, secondary malignancies, and death were uncommon, although the follow-up time in this study was relatively short.     

Treatment of early stage Hodgkin's disease with radiation therapy plus short-cycle (3 MOPP) adjuvant chemotherapy

Eighty-four consecutive, previously untreated patients with stage I, II A-B and IIIA Hodgkin's disease were treated with combined modality therapy including subtotal or total nodal irradiation, followed by three cycles of MOPP. MOPP was administered before radiotherapy in patients with systemic symptoms or with bulky disease. Seventy-six of 84 patients (90.5%) achieved complete remission, and 8 died from disease progression after a variable period of incomplete remission. Three of 76 (3.9%) relapsed, and 2 of them have been subsequently salvaged. Up to the present time, 70 patients are alive, without evidence of disease; 9 have died from Hodgkin's disease, 2 from acute non-lymphoblastic leukemia, and 3 from intercurrent causes. No death occurred from acute toxicity due to chemotherapy. Actuarial overall survival is 82.3% and freedom from relapse is 81.8% after 48 months' median observation (range: 12-111 months). No significant difference in survival and freedom from relapse has been observed with respect to age, sex, stage, presence or absence of unfavorable prognostic factors. The role of adjuvant chemotherapy and its use in a reduced number of cycles in early stage Hodgkin's disease are discussed.     

Sexual dysfunction and treatment for early stage cervical cancer

Assessment of sexual frequency, function, and behavior, as well as martial happiness and psychological distress was performed for 61 women with early stage, invasive cervical cancer at the time of diagnosis. Cancer treatment was radical hysterectomy alone for 26 women and radiotherapy with or without surgery for 37. Followups took place at 6 and 12 months after cancer therapy. Women's sexual satisfaction, capacity for orgasm, and frequency of masturbation remained stable, whereas frequency of sexual activity with a partner and range of sexual practices decreased significantly by one year. Women who received irradiation with or without surgery resembled women who underwent radical hysterectomy alone at 6 months. By one year, however, the radiotherapy group had developed dyspareunia, which was reflected in gynecologist ratings at pelvic examination. The women receiving radiotherapy also had more problems with sexual desire and arousal, and were less likely to resume several daily life activities. Cancer treatment modality was not related to marital happiness or stability, however.     

Long-term morbidity of adjuvant whole abdominal radiotherapy (WART) or chemotherapy for early stage ovarian cancer

The aim of the study was to evaluate long-term toxicity of adjuvant treatment in early stage ovarian cancer survivors. Data from all patients treated in one hospital for early stage ovarian cancer diagnosed between 1980 and 1990 were collected using a structured data form. In 93 FIGO stages I and II patients, cytoreductive and staging surgery was performed; 15 received no adjuvant treatment (controls), 39 whole abdominal radiotherapy (WART) and 39 platin-based chemotherapy. Median age at diagnosis was 54 years (range 21–83 years). During follow-up, 49/93 (53%) patients have died with a median overall survival of 18.4 years (95% CI 12.8–23.9). In both the radiotherapy and the chemotherapy group, 50% of patients reported long-term side-effects (all grades) versus 13% of controls. Two patients in the WART group died from bowel complications. Secondary malignancies were observed in 16 patients. Of all patients alive at the last follow-up, 12/17 (71%) patients treated with radiotherapy and 11/18 (61%) treated with chemotherapy experienced long-term morbidity versus 2/9 (22%) controls (P = 0.03).In conclusion: Long-term follow-up of early stage ovarian cancer patients showed lasting GI morbidity in the survivors treated with adjuvant radiotherapy, which has therefore become obsolete. Cisplatin-based chemotherapy caused peripheral neuropathy versus virtual absence of problems in the survivors of just surgery, emphasising the need for strict criteria before instigating adjuvant treatment.     

乳腺癌保乳治疗的现状和展望

本文介绍早期乳腺癌保乳治疗的现状和进展,主要从乳腺癌病理生理特点、保乳治疗与根治性手术的等效性、保乳手术的技术要求、前哨淋巴结活检、局部复发的相关风险因素和术后放疗等几个方面加以探讨。随着乳腺癌早期发现比例的逐渐提高和医患观念的更新,乳腺癌保乳治疗的应用前景将更加广阔。     

Surgical management of early stage lung cancer

For patients with lung cancer, the greatest hope for cure rests with patients with early stage disease. Surgery has been the standard of care for this group with the best 5-year survival of only 65% being achieved in patients with earliest pathologic Stage IA disease. Using strategies gained from the management of patients with advanced disease, clinicians are investigating the use of perioperative chemotherapy and radiotherapy to improve survival. In addition, biologic and molecular markers are being evaluated to assist in predicting prognosis and to identify those patients at increased risk for recurrent disease. Postoperative surveillance of patients using helical computed tomography (CT) scanning is being investigated to detect early recurrences and second primary lesions. With such treatment and management plans on the horizon, the prognosis of patients with early stage non-small cell lung cancer (NSCLC) may be improved.     

早期高危宫颈癌术后同期放化疗研究进展

宫颈癌是常见妇科恶性肿瘤之一,位居全球2012年新发病例和死亡病例第四位。早期高危宫颈癌术后需要辅助治疗。术后同期放化疗较术后单纯放疗降低盆腔外复发率并提高生存率,较术后序贯放化疗延长中位生存时间和生存率。术后同期放化疗后巩固性化疗较术后单纯同期放化疗提高生存率。回顾性研究表明术后同期放化疗与术后单纯化疗疗效相当,但仍需进一步研究。影响术后同期放化疗疗效的因素主要包括化疗方案、放疗技术、手术与同期放化疗的时间间隔、多发盆腔淋巴结转移和盆腔淋巴结清扫个数等。术后同期放化疗不良反应主要包括血液学不良反应和胃肠道不良反应,其中血液学不良反应最常见。放疗技术的进步可改善不良反应发生率。