Angiosarcoma of the scalp treated with curative radiotherapy plus recombinant interleukin-2 immunotherapy

PURPOSE: To evaluate the effectiveness of curative radiotherapy (RT) plus recombinant interleukin-2 (rIL-2) immunotherapy regarding the treatment results for angiosarcoma of the scalp. Curative resection of angiosarcoma of the scalp is usually difficult because of the diffuse, clinically undetectable local spread. RT is a rational therapeutic approach, because a wide region of the dermis can be treated, while sparing the underlying normal tissues. Recently, the effectiveness of immunotherapy with rIL-2 has also been reported in the treatment of angiosarcoma of the scalp. METHODS AND MATERIALS: The data of 20 patients with angiosarcoma of the scalp treated with curative RT plus rIL-2 immunotherapy between January 1988 and June 2002 were retrospectively analyzed. The total radiation dose was 70.3 +/- 6.9 Gy. The fractions were 2-3 Gy daily, given 5 d/wk. rIL-2 immunotherapy was performed by transcatheter arterial administration in 10 patients, systemic administration in 11 during the course of RT, and intratumoral injection in 10 during and/or after RT; 12 patients received a combination of two. Five patients underwent limited surgery, and concomitant pacilitaxel chemotherapy was also used in 2 patients. RESULTS: The median survival time for overall, local recurrence-free, and distant metastasis-free survival was 36.2, 11.1, and 17.8 months, respectively. Local recurrence developed in 7 patients (35%), 4 of whom also had evidence of distant metastases. An additional 7 patients (35%) developed distant metastases alone. Recurrence within the radiation field was recognized in 2 patients with systemic rIL-2 administration alone (p < 0.05). Arterial or intratumoral administration combined with systemic administration of rIL-2 resulted in better distant metaststasis-free survival rates (p < 0.05). CONCLUSION: Curative RT plus rIL-2 immunotherapy provided an efficient, effective means of treating angiosarcoma of the scalp. Arterial or intratumoral administration combined with systemic administration of rIL-2 may prolong survival. Additional studies with detailed treatment protocols are recommended.     

High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions

PURPOSE: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. METHODS AND MATERIALS: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. RESULTS: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. CONCLUSION: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.     

Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ

The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of 90 women with local only first failure (n=85) or local-regional only first failure (n=5). The histology at the time of recurrence was invasive carcinoma for 53 patients (59%), non-invasive carcinoma for 34 patients (38%), angiosarcoma for one patient (1%), and unknown for two patients (2%). The median follow-up after salvage treatment was 5.5 years (mean=5.8 years; range=0.2-14.2 years). The 10-year rates of overall survival, cause-specific survival, and freedom from distant metastases after salvage treatment were 83%, 95%, and 91%, respectively. Adverse prognostic factors for the development of subsequent distant metastases after salvage treatment were invasive histology of the local recurrence and pathologically positive axillary lymph nodes. These results demonstrate that local and local-regional recurrences can be salvaged with high rates of survival and freedom from distant metastases. Close follow-up after initial breast conservation treatment with radiation is warranted for the early detection of potentially salvageable local and local-regional recurrences.     

Metabolic (FDG-PET) response after radical radiotherapy/chemoradiotherapy for non-small cell lung cancer correlates with patterns of failure

BACKGROUND: We previously reported that F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) response correlated strongly with survival after radical radiotherapy (RT)/chemoradiotherapy for non-small cell lung cancer (NSCLC). PET-response, survival and patterns of failure data are presented with long-term follow-up. METHODS: Pre- and post-treatment FDG-PET scans were performed for 88 patients after concurrent platinum-based radical chemo/RT (n = 73) or radical RT alone (n = 15). PET responses were prospectively assessed as either complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD). RESULTS: RT was 60 Gy in 30 fractions in 6 weeks. Follow-up PET was performed at a median of 70 days after treatment. PET responses were: CMR, n = 40 (45%); PMR, n = 32 (36%); SMD, n = 5 (6%) and PMD 11 (13%). Estimated median survival after follow-up PET was 23 months; median follow-up duration 35 months. One and 2 year survival after follow-up PET was 68% and 45%, respectively. Median survival for CMR and non-CMR patients was 31 and 11 months, respectively (p = 0.0001). One-year survival for CMR and non-CMR patients was 93% and 47%, respectively and 2 years survival was 62% and 30%, respectively. Excluding PMD patients, non-CMR patients had higher rates of local failure (HR 2.15, p = 0.009) and distant metastasis (HR 2.05, p = 0.041) than CMR patients. By last follow-up, 20 of 40 CR patients (50%) had PMD, with local failure (n = 8), distant metastasis (n = 2) or both (n = 10). CONCLUSIONS: Attainment of CMR after radical RT/chemoRT for NSCLC bestows superior freedom from local and distant relapse; late local relapse is common.     

Salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ of the breast

BACKGROUND: The purpose of the current study is to evaluate the outcome of salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. METHODS: An analysis was performed of 42 patients with local only first failure (n = 41) or local-regional only first failure (n = 1) after breast-conserving surgery and radiation treatment had been given for DCIS of the breast. Surgical treatment at the time of local recurrence included mastectomy (n = 37; 88%) or excision (n = 5; 12%). Adjuvant systemic therapy at the time of local recurrence was chemotherapy (n = 3; 7%), tamoxifen (n = 8; 19%), both (n = 1; 2%), none (n = 29; 69%), or unknown (n = 1; 2%). The median interval from the time of initial treatment to local recurrence was 4.8 years (range = 1.0-15.2 yrs). The median follow-up after salvage treatment was 4.5 years (range = 0.2-12.8 yrs). RESULTS: At the time of the local recurrence, 22 patients (52%) had invasive ductal carcinoma, 18 patients (43%) had DCIS, 1 patient (2%) had invasive lobular carcinoma, and 1 patient (2%) had angiosarcoma. After salvage treatment, the rate of overall survival and the rate of cause specific survival for all 42 patients were 92% at both 5- and 8-years after treatment. The rate of freedom from distant metastases was 89% at 5 and 8 years. Favorable prognostic factors after salvage treatment were DCIS as the histology of the local recurrence and mammography only as the method of detection of the local recurrence. CONCLUSIONS: The results of salvage treatment in the current study demonstrated that local recurrences were salvaged with high rates of survival and freedom from distant metastases. These results support the use of breast-conserving surgery and radiation for initial management of DCIS of the breast.     

Can elective nodal irradiation be omitted in stage III non-small-cell lung cancer? Analysis of recurrences in a phase II study of induction chemotherapy and involved-field radiotherapy

PURPOSE: To establish the recurrence patterns when elective mediastinal irradiation was omitted, patients with Stage III non-small-cell lung cancer were treated with sequential chemotherapy (CHT) and involved-field radiotherapy (RT). METHODS AND MATERIALS: Fifty patients were treated with either two or four cycles of induction CHT, followed by once-daily involved-field RT to 70 Gy, delivered using three-dimensional treatment planning. The contoured gross tumor volume consisted of the pre-CHT tumor volume and nodes with a short-axis diameter of > or = 1 cm. Patients were reevaluated at 3 and 6 months after RT using bronchoscopy and chest CT. Elective nodal failure was defined as recurrence in the regional nodes outside the clinical target volume, in the absence of in-field failure. RESULTS: Of 43 patients who received doses > or = 50 Gy, 35% were disease free at last follow-up; in-field recurrences developed in 27% (of whom 16% had exclusively in-field recurrences); 18% had distant metastases exclusively. No elective nodal failure was observed. The median actuarial overall survival was 18 months (95% confidence interval 14-22) and the median progression-free survival was 12 months (95% confidence interval 6-18). CONCLUSION: Omitting elective mediastinal irradiation did not result in isolated nodal failure. Future studies of concurrent CHT and RT for Stage III non-small-cell lung cancer should use involved-field RT to limit toxicity.     

Is there a "curative" role of radiotherapy for clinically localized hormone refractory prostate cancer?

Whether definitive radiotherapy (RT) is still an option for patients with clinically prostate-confined prostate cancer treated with androgen deprivation (AD) alone who develop a rising prostate-specific antigen (PSA) is not clear. In this retrospective series, we report the outcome of 29 such patients treated with "curative" radiotherapy at our institution between 1991 and 2000. At initial diagnosis, all patients had evidence of prostate-confined disease and for several reasons underwent AD alone. Afterward all patients developed rising PSA, but again, without clinical evidence of distant/pelvic node disease. All underwent RT with curative intent up to 70 Gy (66 to 76 Gy). Median follow-up after radiotherapy is 33.1 month (range: 7-134.2 months). For living patients, minimum and median follow-ups are 30.4 and 55.4 months, respectively. Twenty-three patients (79%) developed overt clinical disease, most of which (19/23, 83%) involved distant sites, whereas isolated locoregional failure was observed in only 4 patients (4/23, 17%). The estimates of locoregional control rate (LRC), actuarial incidence of distant metastases, and overall survival at 5 years are 89 +/- 7%, 68 +/- 9%, and 28 +/- 9%, respectively. Although we were unable to find any predictor of LRC at univariate analysis, patients with low Gleason score at diagnosis, lower PSA at RT, lower risk category and advanced age were less likely to develop distant disease. RT has a palliative role, because most patients with still presumed localized hormone refractory prostate cancer will develop distant metastases. A subset of patients, those with more differentiated tumor at diagnosis and with pre-RT PSA less than 20 ng/mL, might be considered for a more aggressive locoregional approach.     

Treatment and outcome of brain metastasis as first site of distant metastasis from breast cancer

Twenty-eight consecutive patients with breast cancer were analyzedwho presented with a single brain metastasis asfirst site of distant metastasis. The response tosurgery with postoperative radiation therapy (RT) (9 patients)and to non-surgical therapy as first-line treatment was100% and 89% respectively with a significant differencein median recurrence-free intervals of 23 months andof 5 months respectively (p=0.033). Retreatmentof a local relapse by surgery (± RT,± chemotherapy) or by non-surgical treatment resulted ina response in 6 of the 7 operatedpatients and in 5 of the 6 non-operatedpatients with a median duration of response of7 months (range 2–20 months) and of 3months (range 2–4 months) respectively. The overall mediansurvival of the 28 patients with a singlebrain metastasis was 16 months (range 2–39 months).The median survival in the primarily operated patientswas 23 months, in the primarily not-operated group10 months, and in the never-operated group 9months. In comparison, the response to non-surgical treatmentin 20 consecutive patients who presented with multiplebrain metastases as first site of distant metastasiswas 55% with a median recurrence free intervalof 4 months. The median survival in thisgroup was 4 months, which was significantly shorterthan survival of patients with single brain metastasis(p=0.0036). These results suggest that breastcancer patients with a single brain metastasis asfirst presentation of relapse constitute a specific subgroupwith a favorable response to treatment and along survival especially if they can be treatedby surgery with postoperative RT.     

Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy

PURPOSE: To analyze a prospective protocol combining surgery, chemotherapy (CT), and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid carcinoma. METHODS AND MATERIALS: Thirty anaplastic thyroid carcinoma patients (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases were present in 18 patients and lung metastases in 6. Surgery was performed before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60 mg/m(2)) and cisplatin (120 mg/m(2)) were delivered before RT and four cycles after RT. RT consisted of two daily fractions of 1.25 Gy, 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum. RESULTS: Acute toxicity (World Health Organization criteria) was Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4, respectively. At the end of the treatment, a complete local response was observed in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7 patients were alive in complete remission, of whom 6 had initially received a complete tumor resection. Overall survival rate at 3 years was 27% (95% confidence interval 10-44%) and median survival 10 months. In multivariate analysis, tracheal extension and macroscopic complete tumor resection were significant factors in overall survival. Death was related to local progression in 5% of patients, to distant metastases in 68%, and to both in 27%. CONCLUSIONS: Main toxicity was hematologic. High long-term survival was obtained when RT-CT was given after complete surgery. This protocol avoided local tumor progression, and death was mainly caused by distant metastases.     

Salvage radiotherapy for palpable, locally recurrent prostate cancer after radical prostatectomy

PURPOSE: A retrospective study to evaluate the outcome of salvage radiotherapy (RT) for clinically apparent, palpable prostate cancer recurrence after radical prostatectomy (RP). METHODS AND MATERIALS: Forty-two patients underwent RT for clinically apparent recurrent prostate cancer after RP between 1993 and 1999. The end points and treatment variables of biochemical disease-free survival were evaluated statistically. RESULTS: The median follow-up was 4.3 years. All 42 patients experienced resolution of clinically detectable recurrence within 1 year after RT. The 5-year biochemical disease-free survival, local control, freedom from distant metastases, and overall survival rate was 27%, 94%, 82%, and 78%, respectively. The initial pathologic stage (T3 or T4; p = 0.04) and interval (<2 years from RP to RT; p = 0.01) were independent predictors of biochemical failure, and RT simulation without contrast (p = 0.05) was nearly significant on multivariate analysis. Three patients (7%) experienced chronic Grade 3 or 4 RT-related toxicity. CONCLUSION: Salvage prostate bed RT for clinically apparent locally recurrent prostate cancer after RP provides effective local tumor control with modest durable biochemical control. Patients irradiated with a better simulation technique were found to have a more favorable outcome. A consensus on a definition of biochemical disease-free survival after salvage RT is critical for meaningful comparison of the available data and to future progress in treating this disease process.     

Patterns of failure following radiation with and without chemotherapy in patients with nasopharyngeal carcinoma

PURPOSE: Aim of this study was to retrospectively evaluate patterns of failure, results, and prognostic factors for patients with nasopharyngeal cancer (NPC) following radiotherapy (RT) with and without concurrent chemotherapy (RCT). PATIENTS AND METHODS: Between 1978 and 1999, a total of 101 patients with NPC were treated in our hospital, of whom 53 received external megavoltage RT alone with a median total dose of 76 Gy (1978-1988), and 48 patients had RCT (1989-1999). For RCT a combination of 5-FU and cisplatin was used together with a median total dose of 72 Gy. Patterns of relapse, survival rates and toxicity as well as prognostic factors were evaluated retrospectively. RESULTS: RCT was associated with a marked reduction in distant metastases: 6/48 (13%) vs. 17/53 (32%) after RT alone. Locoregional tumor persistence was only marginally lower with RCT: 10/48 (21%) vs. 17/53 (32%) following RT. Patients with RCT demonstrated a survival advantage compared to those with RT alone (5-year overall survival (OS): 64% vs. 44%, p = 0.1). OS, disease-specific survival and locoregional control rates were 53, 57, and 78% at 5 years and 47, 51 and 78% at 10 years, respectively. OS was significantly affected by histology (p = 0.007), the patients' age (p = 0.009) and gender (p = 0.01). CONCLUSION: This retrospective study provides further evidence that both reduction of distant metastasis and enhanced local tumor control by combined radiochemotherapy may be associated with improved survival rates in NPC compared to radiation alone. Concurrent RCT is therefore considered the preferable treatment option, however, confirmation in randomized trials is still warranted.     

Malignant Pleural Mesothelioma in Singapore

Aim: To examine the clinical characteristics and outcomes of malignant pleural mesothelioma (MPM) inSingapore. Methods and Materials: A retrospective case note review of patients diagnosed with MPM between1997 and 2007. Overall survival (OS), locoregional recurrence-free survival (LRS) and metastasis-free survival(MFS) were estimated using Kaplan Meier method and comparison were done using log rank test. Multivariateanalysis was not done due to the small number of patients. Results: There were 39 patients diagnosed with MPM.Fifty-nine percent of patients presented with Stage III and IV disease. Eight (21%) patients had surgery with2 patients receiving trimodality treatment and adjuvant chemotherapy respectively. Three patients receivedadjuvant RT and one patient had no adjuvant therapy. Twelve patients received palliative RT or chemotherapy.Median follow-up was 27.0 weeks. Median overall survival (OS) for all patients was 8.0 months (95% CI 6.3-9.7).One-year and 2-year OS were 25.6% and 6.4% respectively. Thirty-eight patients died of progressive diseaseand one patient died of other cause. Locoregional recurrences and distant metastases occurred in 3/8 and 5/8surgically treated patients respectively. Overall, distant metastases occurred in 44% of patients. Surgery didnot affect survival outcomes although patients with dual modality treatment showed a trend towards improvedsurvival. Epithelioid tumours had better prognosis (median OS 10.2 months) compared to biphasic (median OS8.0 months) and sarcomatoid tumours (median OS 1.4 months). Conclusion: Future management of MPM willneed to emphasize on both locoregional and systemic control and hence, inclusion of patients in clinical trialsfor multimodality treatment should be encouraged.     

Pre-operative chemoradiotherapy with oral tegafur-uracil and leucovorin for rectal cancer

BACKGROUND: To evaluate the efficacy and toxicity of pre-operative radiotherapy (RT) combined with oral tegafur-uracil (UFUR) plus leucovorin (LV) in rectal cancer. PATIENTS: Sixty-five patients with rectal adenocarcinoma (clinical staged T2-4N0-2M0) received pelvic RT of 45 Gy in 20 fractions over 28 days. Concurrent chemotherapy consisted of UFUR (200 mg/m(2)/day) and LV (45 mg/day) on day 1-28. UFUR (250 mg/m(2)/day) and LV were continued on day 36-63. Surgery was performed on day 70. RESULTS: Sixty-three patients completed the concurrent chemoradiotherapy (CCRT) and 56 received curative or palliative surgery. Among the 52 patients receiving curative resection, downstaging (DS) occurred in 39 (75%), pathological complete response in 13 (25%), and sphincter preservation was achieved in 16 of 29 (55%) with lower-seated tumors. With a median follow-up time of 33 months, local failure developed in 4 (8%) and distant metastases occurred in 7 (14%). The 3-year overall survival was 92% and disease-free survival 76%. For all 65 patients, grade 3-4 diarrhea developed in 6 (9%) and grade 3-4 leucopenia observed in 2 (3%). CONCLUSIONS: Oral UFUR + LV administered with pre-operative RT are effective in tumor DS, pathological complete response, and sphincter preservation with tolerable toxicity in rectal cancer.     

Surgical therapy for distant metastases of malignant melanoma

BACKGROUND: Manifestation of distant metastases in melanoma patients commonly indicates a poor prognosis. The aim of the current study was to examine the role of surgical treatment in these patients. METHODS: Data from 444 patients with distant melanoma metastases were gathered prospectively from January 1978 through December 1997. Characteristics of the primary tumor, time until the first occurrence of distant metastases, frequency and site of distant metastases, surgical therapy, and survival were evaluated by univariate and multivariate analyses. RESULTS: Histology, Breslow thickness, Clark level, and pT and pN categories (UICC 1997) significantly influenced the median interval from initial diagnosis to manifestation of distant metastases. The most common single localization was the lung (n = 83), followed by distant lymph node (n = 79), and skin metastases (n = 51). One hundred seventy-four patients received surgical treatment (39%) and 111 (25%) patients received surgical treatment with curative resection (R0, UICC 1997), most frequently in distant lymph node or skin metastases (57% and 59%, respectively). Median survival time and 2-year survival rate for all patients were 7 months and 15.8%, respectively, 17 months and 36.1% following curative resection, 6 months and 12.7% after incomplete resection (n = 63) (P < 0.0001). Conservatively treated patients survived for a median of only 4 months with a 2-year survival of 8.1%. Multivariate survival analysis showed localization of the primary tumor (head/neck/trunk vs. extremities), the number of involved sites, and surgical therapy to be independent prognostic factors. CONCLUSIONS: Surgical therapy of distant metastases was most beneficial when complete removal of metastatic tissue was achieved. Selection of patients for surgical excision should be determined by individual patient indications.     

Excellent local control rates and distinctive patterns of failure in myxoid liposarcoma treated with conservation surgery and radiotherapy

PURPOSE: To evaluate the local control rates and patterns of metastatic relapse in patients with localized myxoid liposarcoma treated with conservation surgery and radiotherapy (RT). PATIENTS AND METHODS: Between 1960 and 2003, 127 patients with non-metastatic myxoid liposarcoma were treated with conservation surgery and RT at our institution. The median patient age was 39 years (range, 14-79 years). Of the 127 patients, 46% underwent preoperative RT (median dose, 50 Gy) and 54% underwent postoperative RT (median dose, 60 Gy). Also, 28% received doxorubicin-based chemotherapy as a part of their treatment. RESULTS: The median follow-up was 9.1 years. The overall survival rate at 5 and 10 years was 87% and 79%, respectively. The corresponding disease-free survival rates were 81% and 73%. The local control rate at > or =5 years was 97%. The actuarial rate of distant metastases at 5 and 10 years was 15% and 24%, respectively. Of the 27 patients who developed distant metastases, 48% did so in the retroperitoneum, 22% in other extrapulmonary soft tissues, 22% in the lung, 15% in bone, and 4% in the liver. CONCLUSION: The results of our study have shown that RT and conservation surgery for localized myxoid liposarcoma provide excellent local control. Distant metastatic relapse tended to occur in the retroperitoneum and other nonpulmonary soft tissues. Therefore, staging and surveillance imaging should include the abdomen and pelvis, as well as the thorax, for patients with localized myxoid liposarcoma.     

Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-and-neck mucosal site treated with radiation therapy alone or in combination with neck dissection

PURPOSE: The present study presents the experience at the University of Florida with treatment of patients with squamous cell carcinomas (SCC) metastatic to cervical lymph nodes from an unknown head-and-neck mucosal (H&NM) site with radiotherapy (RT) alone or in combination with neck dissection (ND). METHODS AND MATERIALS: The study included 126 patients treated with curative intent from 1964 to 1997. All patients had follow-up for at least 2 years. No patients were lost to follow-up. RESULTS: Twelve patients (10%) developed SCC in H&NM sites at 0.5 to 10.9 years (median, 1.8 years). The rate of developing carcinomas in H&NM sites at 5 years was 13%. Histologic differentiation significantly affected the rate of developing carcinomas in H&NM sites in multivariate analysis. Sixteen patients (13%) had persistent nodal disease and 12 patients (10%) developed recurrent nodal disease at 0.5 to 10.9 years (median, 1.1 years). The nodal control rate at 5 years was 78%. Nodal size, N stage, and planned ND significantly affected the rate of nodal control in multivariate analysis. Nineteen patients (15%) developed distant metastasis at 0.2-5.1 years (median, 0.9 years). The distant metastases rate at 5 years was 14%. Extracapsular extension and RT dose significantly affected the risk of distant metastases in multivariate analysis. The overall absolute survival rate at 5 years was 47%. Extracapsular extension, N stage, RT dose for H&NM sites, and planned ND significantly affected absolute survival in multivariate analysis. The rate of cause-specific survival at 5 years was 67%. Extracapsular extension, nodal size, N stage, overall treatment time, and planned ND significantly affected cause-specific survival in multivariate analysis. Eight patients (6%) had severe postoperative complications and 6 patients (5%) had severe late complications. CONCLUSION: The present study supports the effectiveness of RT in lowering the rate of developing carcinomas in the H&NM sites.     

淋巴结阳性胸段食管鳞癌术后放化疗临床研究

目的 对淋巴结阳性胸段食管鳞癌术后放化疗与术后放疗进行回顾性分析,观察其疗效和不良反应.方法 选择首程治疗行胸段食管鳞癌三野淋巴结清扫根治术,术后病理有淋巴结转移、无远处转移患者304例,其中术后放疗组140例,术后放化疗组164例.术后放疗剂量50 Gy,化疗方案为顺铂加紫杉醇,21 d为1个周期,平均2.35个周期/例.结果 术后放化疗组和术后放疗组3年总生存率、无瘤生存率分别为65.7%和52.8%(χ2=6.90,P=0.009)、62.5%和52.8%(χ2=4.75,P=0.029);锁骨上区淋巴结转移率、远处转移率、总复发转移率分别为1.8%和7.1%(χ2=5.21,P=0.022)、18.3%和27.9%(χ2=3.94,P=0.047)、27.4%和39.3%(χ2=4.80,P=0.028);早期不良反应的中性粒细胞减少、放射性食管炎、胃肠道反应分别为96.3%和32.1%(χ2=140.31,P=0.000)、37.2%和26.4%(χ2=4.01,P=0.045)、23.2%和5.0%(χ2=19.77,P=0.000);晚期不良反应分别为6.1%和5.0%(χ2=0.17,P=0.678).结论 淋巴结阳性胸段食管鳞癌术后放化疗能提高生存率和无瘤生存率,降低锁骨上区淋巴结转移率、远处转移率和总复发转移率,早期不良反应重于单纯术后放疗,但患者能耐受治疗.

Abstract：

Objective To retrospectively analyze the treatment results and side effects of postoperative chemoradiotherapy and postoperative radiotherapy of thoracic esophageal squamous cell carcinoma (EPC) with positive lymph nodes.Methods Three hundred and four patients of thoracic EPC were initially treated with three-field lymphadenectomy, with pathological positive lymph nodes and without distant metastases;and randomly divided into two groups:140 patients of the simple postoperative radiotherapy (RT) and 164 patients of postoperative chemoradiotherapy (CRT).The median total dose was 50 Gy.The regimen of concurrent chemotherapy included cisplatin and taxol, and the intermission was 21 days;the median cycles were 2.35.Results The 3-year overall survival rates were 65.7% of CRT and 52.8% of RT (χ2=6.90,P=0.009), and The 3-year disease-free survival rates were 62.5% of CRT and 52.8% of RT (χ2=4.75,P=0.029).The incidences of the supraclavicular lymph-node metastases were 1.8% and 7.1%(χ2=5.21,P=0.022), respectively;and the incidences of distant metastases were 18.3% and 27.9%(χ2=3.94,P=0.047), respectively;and the incidences of overall metastases and recurrences were 27.4% and 39.3%(χ2=4.80,P=0.028), respectively.Early side effects included granulopenia (96.3% and 32.1%,χ2=140.31,P=0.000), radiation-induced esophagitis (37.2% and 26.4%,χ2=4.01,P=0.045),and gastrointestinal toxicity (23.2% and 5.0%,χ2=19.77,P=0.000).Late side effects were 6.1% and 5.0%(χ2=0.17,P=0.678), respectively.Conclusions Postoperative chemoradiotherapy of thoracic EPC with positive lymph nodes can improve the overall survival and disease-free survival, decrease the incidence of the supraclavicular metastases, the distant metastases, the total metastases and recurrences.More severe early side effects were observed in chemoradiotherapy than in the radiotherapy group,but well tolerated.     

Radiochemotherapy in the conservative treatment of anal canal carcinoma: retrospective analysis of results and radiation dose effectiveness

PURPOSE: This retrospective analysis reports the results on patients with anal canal carcinoma treated by combined radiotherapy and chemotherapy. METHODS AND MATERIALS: Between March 1993 and December 2001, 43 patients with anal canal carcinoma were treated with radiochemotherapy at the Hospital do Cancer A.C. Camargo. Stage distribution was as follows: I, 3 (7%); II, 23 (53.5%); IIIA, 8 (18.6%); and IIIB, 9 (21%). The median age was 56 years (range, 36-77 years) with most patients being women (4:1). External radiotherapy (RT) was delivered at the whole pelvis followed by a boost at the primary tumor. The median dose of RT at the whole pelvis and at the primary tumor was 45 Gy and 55 Gy, respectively. Chemotherapy was carried out during the first and last 4 days of RT with continuous infusion of 5-fluorouracil (1000 mg/m(2)) and bolus mitomycin C (10 mg/m(2)). Median overall treatment time was 51 days (range, 30-129 days). Thirty-four patients (79%) did not receive elective RT at the inguinal region. Patient's age, tumor stage, overall treatment time, and RT dose at primary tumor were variables analyzed for survival and local control. RESULTS: Median follow-up time was 42 months (range, 4-116 months). Overall survival and colostomy-free survival at 5 years was 68% and 52%, respectively. Overall survival according to clinical stage was as follows: I, 100%; II, 82%; IIIA, 73%; and IIIB, 18% (p = 0.0049). Complete response was observed in 40 patients (93%). Local recurrence occurred in 9 (21%) patients, and of these, 6 were rescued by surgery. Local control with a preserved sphincter was observed in 34 patients (79%). According to the RT dose, local control was higher among patients who received more than 50 Gy at primary tumor (86.5% vs. 34%, p = 0.012). Inguinal failure was observed in 5 patients (15%) who did not receive inguinal elective RT. Distant metastasis was observed in 11 patients (25.6%). Temporary interruption of the treatment as a result of acute toxicity was necessary in 12 patients (28%). Four patients developed mild chronic complications. CONCLUSIONS: This analysis suggests that the treatment scheme employed was effective for anal sphincter preservation and local control; however, the incidence of distant metastases was relatively high. The clinical stage was the main prognostic factor for overall survival. Local control was higher in patients treated with doses of more than 50 Gy at primary tumor. The high incidence of inguinal failure implies the need for elective RT in this region.     

Ⅳ期非小细胞肺癌287例放疗后的生存分析

背景与目的:很多Ⅳ期非小细胞肺癌(non-smallcelllungcancer,NSCLC)的患者需要放疗,特别是对脑、骨转移者放疗有很好的治疗作用。本研究旨在分析放疗对Ⅳ期NSCLC患者生存的影响。方法:对287例资料完整的Ⅳ期NSCLC放疗患者进行回顾性分析。脑放疗为平行对穿两野全脑照射,骨放疗为单野局部照射,对原发灶、区域淋巴结和其它转移部位用2维常规分割或3维适形放疗(3dimensionalconformalradiotherapy,3D-CRT)。脑和骨放疗通常采用4周20次共40Gy或2周10次共30Gy的治疗方案,原发灶和区域淋巴结的中位照射剂量是50Gy(20～70Gy),其它转移部位的中位照射剂量是46Gy(40～60Gy)。结果:全部患者中位生存期9个月(8～10个月),1年和2年生存率分别是30.2%和8.9%。有化疗和无化疗者中位生存期分别为10个月和8个月(P=0.049)。有脑转移、骨转移、其它转移者中位生存期分别为8个月、9个月、10个月,1年生存率分别24.8%、28.7%和37.5%,2年生存率分别为6.7%、7.0%和15.3%。单因素分析发现对生存有显著影响的因素为病理类型和年龄。腺癌患者的生存期高于鳞癌和其它病理类型,中位生存期分别为10个月、7个月、9个月(P=0.046);≤60岁的患者生存期显著高于>60岁的患者,中位生存期分别为11月、8个月(P=0.012);单纯骨转移患者的中位生存期要大于合并有其它转移者(10个月与6个月,P=0.033),而单纯脑转移和同时合并有其它转移的两组患者中位生存期却无明显差异(9个月与8个月,P=0.3742);肿瘤原发灶和区域淋巴结是否放疗对患者生存时间影响不大(10个月与8个月,P=0.066);是否伴有其它慢性疾病对患者的生存期无明显影响(9个月与10个月,P=0.306)。对脑和骨转移的患者采用4周20次40Gy或2周10次30Gy放疗对生存期无明显影响。结论:病理类型、年龄对Ⅳ期NSCLC患者的放疗疗效有显著影响,全脑和骨转移采用4周20次40Gy或2周10次30Gy放疗对生存期无明显影响。     

Mature survival results with preoperative cisplatin,protracted infusion 5-fluorouracil,and 44-Gy radiotherapy for esophageal cancer

PURPOSE: To assess the long-term survival results after cisplatin, protracted infusion 5-fluorouracil, and concurrent radiotherapy (RT) followed by surgical resection of esophageal cancer. METHODS AND MATERIALS: Ninety-two patients with esophageal cancer (65 with adenocarcinoma and 27 with squamous cell carcinoma) were treated in two sequential protocols of preoperative chemoradiotherapy. The patients had tumor confined to the esophagus and regional nodes, including celiac nodes for middle and distal lesions. In trial A (1989-1994), 50 patients were treated with 44 Gy RT (2 Gy/d) along with concurrent 5-fluorouracil 300 mg/m(2)/d given by protracted venous infusion on Days 1-30 and cisplatin 26 mg/m(2) on Days 1-5 and 26-30. In trial B (1995-1997, 42 patients), the chemotherapy dosages during RT were reduced to 5-fluorouracil 225 mg/m(2)/d protracted venous infusion and cisplatin 20 mg/m(2)/d on Days 1-5 and 16-30; three cycles of paclitaxel 135 mg/m(2)and cisplatin 75 mg/m(2) were given postoperatively. Surgery generally occurred 4-6 weeks after completion of the planned preoperative therapy. Transhiatal resection was performed whenever possible. RESULTS:Of the 92 patients, 86 (93%) underwent surgery (1 refused, 2 died preoperatively, and 3 developed evidence of metastatic disease). Of the 92 patients, 80 (87%) had complete resections with negative margins (3 had positive margins and 3 had distant metastases discovered at surgery). The pathologic complete response rate was 33% (30 of 92). The median follow-up was 63.5 months. The median survival and disease-specific survival for all enrolled patients was 35 and 59 months, respectively. The 5-year survival and disease-specific survival rate was 40% and 49%, respectively. Patients with a pathologic complete response had a 67% survival rate at 5 years (median not reached), and the remainder of patients had a 5-year survival rate of 27% (median 21 months; p <0.001). For 21 patients alive after 5 years (60-121 months), 2 died of their disease and all others were disease free. Eight patients with pathologic Stage I tumor at the time of surgery had survival similar to those with a complete response to preoperative therapy. The median survival for patients with pathologic Stage IIA, IIB, III, and IV disease at the time of surgery was 22, 13.5, 18, and 4.9 months, respectively. The pattern of initial failure was local/regional alone in 6% (5 of 90), local/regional plus distant in 3% (3 of 90), and distant alone in 47% (42 of 90). No differences were noted in survival or response rate between those with adenocarcinoma or squamous cell carcinoma. CONCLUSION: The promising 5-year survival results and low rate of late cancer-related deaths suggest that these regimens of intensive neoadjuvant therapy may improve the overall cure rate. The pathologic stage after neoadjuvant therapy is an important predictor of survival and may be useful in selecting patients for novel adjuvant therapies. Isolated local failure is uncommon, indicating that efforts to improve the therapeutic outcome should focus on optimizing systemic therapy rather than intensifying the RT. Additional randomized data are needed to assess the benefits of this therapeutic approach fully.