Guidelines for the treatment of lung cancer with lymph node involvement

Lung cancer with mediastinal lymph node involvement has a poor prognosis, especially when treated with surgery alone. Such cases are considered to be managed best by multimodality treatment. Some randomized trials showed positive results of induction chemotherapy and adjuvant chemotherapy in locally advanced lung cancer, but more evidence is needed to create the standard treatment for stage III lung cancer. A combination of chemotherapy and radiotherapy remain the standard of care for patients with obvious N2 disease, and the role of surgery following induction chemotherapy or chemo-radiotherapy in advanced stage III patients will be evaluated in phase III trials. Enrollment of patients in prospective clinical trials is strongly recommended to clarify unresolved issues in this clinical setting.     

Role of chemotherapy in the management of advanced thymic tumors

Chemotherapy has an important role in the treatment of advanced thymic tumors. Early stage tumors are successfully treated with surgery. Locally advanced tumors (Masaoka stage III and IVA) are often treated with combined modality treatment including surgery, radiation, and chemotherapy. For patients with curable thymic tumors, the ability to attain a complete resection is a critical prognostic factor. Locally advanced tumors have a relatively high risk of recurrence and decreased rates of long-term survival. A multimodality approach including induction chemotherapy and postoperative radiation therapy can improve complete resection rates and long-term outcomes. Thymic tumors are chemoresponsive with optimal responses achieved with cisplatin-based combination chemotherapy. Chemotherapy with radiation can result in long-term progression-free survival for patients with locally advanced disease who remain inoperable following induction therapy. Patients with disseminated (stage IVB) thymic tumors can also have significant disease response and palliation of symptoms when treated with chemotherapy. Octreotide and corticosteroids also have shown efficacy. For best results, it is important that thoracic surgeons, radiation oncologists, and medical oncologists work together to obtain the best local control of tumor and optimal treatment of metastases.     

Neoadjuvant Chemotherapy Followed by Radical Surgery in Patients Affected by FIGO Stage IVA Cervical Cancer

Background Concomitant chemoradiotherapy represents the standard treatment for patients affected by locally advanced cervical cancer. Survival rates in patients affected by FIGO stage IVA disease remain poor. Some authors have suggested that neoadjuvant chemotherapy followed by radical surgery might be a valid alternative to standard treatment. The objective of this study was to analyze the feasibility and results obtained by neoadjuvant chemotherapy in patients affected by stage IVA disease. Methods Eighteen patients affected by FIGO stage IVA cervical cancer were treated with 175 mg/m² paclitaxel and 75 mg/m² cisplatin every 21 days for three courses followed by radical surgery when feasible. Results All patients were subjected to the three planned chemotherapy courses. Two patients achieved a complete clinical response, and 10 patients achieved a partial clinical response. Ten patients were subjected to anterior pelvic exenteration, whereas the remaining eight patients were treated with chemotherapy, radiotherapy, and concomitant chemoradiotherapy. The estimated 3-year and 5-year overall survival rates were 47.4% and 31.6%, respectively. Patients eligible for surgery benefited from significantly longer survival rates. Conclusions Neoadjuvant chemotherapy followed by radical surgery is feasible in approximately half of patients affected by FIGO stage IVA cervical cancer. Overall survival rates appear similar to those reported with concomitant chemoradiotherapy. Patients who are amenable to radical surgery after chemotherapy may benefit from long-term survival rates.     

Primary surgery as treatment for early squamous cell carcinoma of the tonsil

BACKGROUND: The management of tonsil carcinoma has gradually evolved such that the literature is replete with outcome summaries of this disease treated with primary RT and chemotherapy. Recently there have been no reports of patient outcomes with primary surgical therapy. Nonsurgical treatment is warranted when tumors are unresectable or if the patient refuses surgery. Our policy has been to treat operable squamous cell carcinoma (SCCA) of the tonsil with surgery. The decision to use adjuvant therapy is based on the surgical and histologic findings. We herein report our results with this treatment protocol. METHODS: A retrospective review of 162 patients with SCCA of the tonsil was performed. Eighty-four patients were treated with surgery, which was followed by RT and/or chemotherapy if histologic signs of aggressive behavior were identified. Patients were followed 2 to 15 years after treatment. RESULTS: Of the 9 patients with stage I disease, 89% are without evidence of recurrent disease and 91% of patients with stage II tonsil cancers are also disease free. The survival rates for stage III and stage IV cancer patients are 79 and 52%, respectively. CONCLUSION: Our data suggest that patients with early tonsil cancer can be effectively treated with surgery. Surgery allows pathologic staging so that patients with advanced tumors can be treated with adjuvant therapy.     

Treatment of nonmetastatic Ewing’s sarcoma family tumors of the spine and sacrum: the experience from a single institution

The objective of this study is to determine the best local treatment combined with neoadjuvant chemotherapy for ESFT of the spine and sacrum, for the best local treatment for Ewing sarcoma family tumors (ESFT) according to the primary site is still unclear. Nowadays surgery is used in local treatment of ESFT, but literature is scarce on the best local treatment in sites where surgery is problematic, such as the spine. This study evaluates the outcome and the rate of local recurrence of ESFT in the spine and sacrum when treated with neoadjuvant chemotherapy, and locally by radiotherapy alone or surgery, followed by reduced doses of radiotherapy. Forty-three patients with nonmetastatic ESFT located in the spine and sacrum were treated at our institution between 1983 and 2000 with neoadjuvant chemotherapy, and locally by radiotherapy alone in 26 cases, and surgery followed by radiotherapy at reduced doses in 17. The 5- and 10-year event-free survival (EFS) was 37 and 30%, and the 5- and 10-year overall survival was (OS) 42 and 32%. The prognosis was unrelated to gender and age, tumor volume, chemotherapy protocol, and local treatment. The outcome seemed worse for patients with primary tumors located in the sacrum than for patients with tumors located in the rest of the spine (5-year EFS = 23 vs. 46%). For these patients the results were significantly worse than for those we achieved with neoadjuvant treatment for ESFT located in other sites. However, no differences were observed between patients locally treated with radiotherapy alone and those treated by radiotherapy followed by surgery. We concluded that regardless of the type of local treatment even when associated with neoadjuvant therapy, ESFT in the spine and sacrum has a poor outcome and prognosis is significantly worse than that of primary ESFT in other sites.     

单中心四肢骨肉瘤311例预后分析

 目的 探讨单中心四肢骨肉瘤的治疗、预后及生存状况。方法 回顾性分析1998年至2008年间单中心收治的311例四肢骨肉瘤患者的病历资料,记录患者的基本资料、化疗、手术、并发症、肿瘤转移及预后情况,应用Kaplan-Meier、Cox regression 等统计学方法分析各变量与预后生存的关系。结果 311例四肢骨肉瘤患者,男206例,女105例;年龄5～56岁,平均18.6岁;上肢29例,下肢282例。282例获得广泛或根治性手术,保肢手术149例,截肢手术133例。术后64例患者发生各种并发症,其中17例出现2次以上的术后并发症,25例发生肿瘤局部复发。105例获得规范化疗,206例未获得规范化疗,5年生存率分别为57.4%和36.3%。肺转移患者(76例)和无肺转移患者5年生存率分别为16.8%和50.7%。Enneking 分期ⅡB期和Ⅲ期患者5年生存率分别为44.6%和33.1%。选择保肢手术和截肢手术患者的5年生存率分别为56.6%和31.8%,由于截肢患者中有较大的比例施行了不规范化疗以及其他混杂因素导致5年生存率明显降低。Cox回归分析显示化疗不规范和发生肺转移患者预后较差。结论 新辅助化疗联合肿瘤广泛或根治性手术切除可以挽救约60%青少年四肢骨肉瘤患者的生命,肺转移和不规范化疗严重影响患者的预后。     

Genitourinary rhabdomyosarcoma

Rhabdomyosarcoma is the most common soft tissue malignant neoplasm involving the pelvis of children. Debate still exists over whether the best treatment is pelvic exenteration, radiation and chemotherapy or chemotherapy as the cornerstone to treatment, with diminished needs for extensive surgery and prolonged radiotherapy. Contrariwise, there is little debate over the combined treatment modality for paratesticular rhabdomyosarcoma. We have evaluated and treated 19 children with rhabdomyosarcoma, including 17 with pelvic rhabdomyosarcoma and 2 with paratesticular rhabdomyosarcoma. This retrospective study was done to evaluate treatment regimens for patients with genitourinary rhabdomyosarcoma. For patients with pelvic rhabdomyosarcoma the study was divided into 2 series. In an early series 6 of 7 children had a pelvic exenteration with or without chemotherapy. Of these 7 children 3 are well 15 to 27 years following diagnosis. In a later series of 10 children, when chemotherapy was used more commonly, none underwent pelvic exenteration. Of these 10 patients 7 had chemotherapy or chemotherapy and biopsy only. Only 1 child, who presented with stage IV disease, died in this series. Another child with stage III disease had progressive disease despite chemotherapy and subsequent cystoprostatectomy. Thus, of 9 remaining patients 8 are well from 1 to 8 years. It appears that pelvic rhabdomyosarcoma can be treated effectively with chemotherapy, and limited surgery and radiation. Fortunately, pelvic exenteration can now be limited to a select few.     

Randomized study of preoperative chemotherapy in squamous cell cancer of the esophagus. CAO Esophageal Cancer Study Group]

Only 46 of 77 patients with potentially resectable squamous cell carcinoma of the esophagus who were asked to participate in a phase-III trial to be treated by either immediate surgery (n = 24) or surgery plus preoperative chemotherapy (n = 22) agreed to randomization. A priori 13 patients chose chemotherapy before surgery and 18 patients only surgery. The complete chemotherapy program consisted of three cycles with 5-FU (1g/m2/d x 5) and cisplatin (20 mg/m2/d x 5). The response rate (CR and PR) to chemotherapy was 47%. Side effects of therapy were higher than expected, based on results of previous phase-II studies. Two drug related deaths were observed. The resectability rate for patients in the operation-only group was 80 and 70% for patients receiving chemotherapy. The postoperative rate of septic complications (41 vs. 26%) and respiratory disorders (37 vs. 26%) were higher for patients with preoperative chemotherapy in comparison to the only surgically treated controls. Surgery related mortality was increased in the chemotherapy group (18%) compared to the controls (10%). Patients responding to preoperative chemotherapy had a prolonged survival (median 13 months) when compared with non-responders (median 5 months), but the median survival for the chemotherapy group and the only-surgery group was identical (10 months). We conclude, that the preoperative chemotherapy regime used in this multi-institutional trial neither influences resectability, nor increases overall survival of patients with localized esophageal cancer. However, preoperative chemotherapy was associated with considerable side effects and a high postoperative mortality.     

Hepatic resection in breast cancer metastases: should it be considered standard treatment?

A 34-year-old woman was diagnosed in October 1994 with a stage I breast cancer and treated with conservative surgery, locoregional radiotherapy and adjuvant chemotherapy. Nonetheless, 47 months after the initial diagnosis, an isolated liver metastasis was diagnosed in segments VII and VIII. A subsegmentectomy was performed, and chemotherapy with doxorubicin and paclitaxel was given for five cycles. High-dose chemotherapy with peripheral stem cell rescue was then administered and tamoxifen hormonal therapy was begun. Now, 54 months after the liver recurrence, the patient remains free of disease. Isolated liver metastases from breast cancer are rare and should be treated with surgical resection if possible, in the context of multimodality programs with hormonal and chemotherapy. According to the small series published in the literature, an improvement of 27-57 months in median survival rates can be expected when such treatment replaces standard therapies, although a selection bias cannot be excluded.     

Multi-modality treatment of non-small cell lung cancer

Despite significant advances in radiation therapy techniques and a variety of newer chemotherapeutic agents, when multimodality treatment for stage I and II tumors has been tested by Phase III randomized prospective trials of adequate size, no significant survival advantage over surgery alone has been found in most instances. Modalities tested include preoperative radiation therapy, and postoperative chemotherapy and radiation therapy. Trials are presently underway to test preoperative chemotherapy for stages Ib, II, and T3NI (S9900) and to test adding surgery for patients with N2 disease who have been treated by chemotherapy and radiation therapy (INT 0139). Results of a recently completed trial (JBR10) will answer the question of whether postoperative chemotherapy is of benefit for patients with stages T2N0 or T1-2N1. Until these trials are completed, surgeons should resist the temptation to use newer but unproven therapies except within established approved protocols.     

Preliminary report of multimodal treatment with ifosfamide, 5‐fluorouracil,etoposide and cisplatin (IFEP chemotherapy) against metastatic adenocarcinoma of the urachus

Abstract: We report the effectiveness of a combination chemotherapy consisting of ifosfamide, 5‐fluorouracil, etoposide and cisplatin (IFEP chemotherapy) against metastatic adenocarcinoma of the urachus. From April 1995 to November 2004, four patients with adenocarcinoma of the urachus who developed metastases after definitive surgery were treated with the IFEP chemotherapy followed by consolidative radiotherapy or salvage surgery in good responders. During the median follow‐up period of 26 months, three of the four patients responded to the regimen (75%). In one patient with pulmonary metastases, four cycles of the IFEP chemotherapy, followed by stereotactic consolidative radiotherapy resulted in a complete remission for more than 8 years. Two patients achieved partial remission after the IFEP chemotherapy. We have demonstrated the IFEP chemotherapy is one of the most effective chemotherapy regimens against metastatic adenocarcinoma of the urachus. A multimodal treatment strategy, even with curative intent, can be considered when a sufficient effect was obtained by the IFEP chemotherapy.     

413例骨肉瘤化疗、手术和预后的10年随访研究

目的对骨肉瘤的化疗、手术及预后进行随访研究,探讨骨肉瘤治疗中影响患者预后、生存及医生治疗决策的因素。方法回顾性调查1998年1月-2008年1月单一骨肿瘤治疗中心注册的413例骨肉瘤患者的病例资料,记录患者的基本情况、手术情况、化疗情况以及随访和预后情况,比较规范化疗和未规范化疗患者局部复发、肺转移率以及生存率的差异,分析骨肉瘤治疗中存在的问题。结果 413例患者中,随访〉5个月352例,失访率14.8%;随访〉12个月251例,失访率39.2%;随访〉60个月216例,失访率47.7%。321例行手术治疗,其中截肢手术165例,保肢手术156例。126例完成规范化疗,287例由于各种原因没有完成规范化疗或未进行化疗。不规范化疗患者肺转移发生率、5年总生存率及5年总无瘤生存率均低于规范化疗患者,差异具有统计学意义（P〈0.05）。结论骨肉瘤的临床治疗存在患者就诊迟、完成规范化疗比例小、保肢率低、失访率高等问题。重视并解决这些问题对骨肉瘤患者的预后有重要意义。     

The optimal time for surgery in women with serous ovarian cancer

BackgroundAdvanced high-grade serous ovarian carcinoma (HGSC) is commonly treated with surgery and chemotherapy. We investigated the survival of patients treated with primary or interval surgery at different times following neoadjuvant chemotherapy. Their survival was compared with that of patients treated with primary cytoreductive surgery and adjuvant chemotherapy.MethodsPatients with stage III or IV HGSC were included in this retrospective cohort study. Clinical data were obtained from patient records. Patients were divided into 2 groups based on treatment with neoadjuvant chemotherapy and interval cytoreductive surgery (NAC) or with primary cytoreductive surgery and adjuvant chemotherapy (PCS). Study groups were stratified by several clinical variables.ResultsWe included 334 patients in our study: 156 in the NAC and 178 in the PCS groups. Survival of patients in the NAC group was independent of when they underwent interval cytoreductive surgery following initiation of neoadjuvant chemotherapy (p < 0.001). Optimal surgical cytoreduction had no impact on overall survival in the NAC group (p < 0.001). Optimal cytoreduction (p < 0.001) and platinum sensitivity (p < 0.001) were independent predictors of improved survival in the PCS but not in the NAC group. Patients in the NAC group had significantly worse overall survival than those in the PCS group (31.6 v. 61.3 mo, p < 0.001).ConclusionWomen with advanced HGSC who underwent PCS had better survival than those who underwent interval NAC, regardless of the number of cycles of neoadjuvant therapy. Optimal cytoreduction did not provide a survival advantage in the NAC group.     

Clinical stage II non-seminomatous germ cell testicular tumours. Results of management by primary chemotherapy

Between 1977 and 1984, 92 patients with clinical Stage II non-seminomatous germ-cell testicular tumours were treated by primary chemotherapy, with surgery reserved for the excision of persisting masses. Eighty patients (87%) are alive and disease-free: 96% for Stages IIA and IIB and 74% for Stage IIC. Of 43 Stage IIA, B and C patients treated with bleomycin, etoposide and cisplatin (BEP), 40 (93%) are disease-free. For the whole group there was a significant difference between the outcome of treatment in patients with retroperitoneal masses greater than 8 cm in transverse diameter compared with those in whom masses were less than 8 cm, the disease-free rates being 54 and 97% respectively. Primary histology did not influence the outcome of treatment. However, whereas 51% of patients with teratocarcinoma had masses resected after chemotherapy, only 26% of embryonal carcinoma patients came to surgery. The results obtained in this series are as good as those obtained when lymph node dissection is employed as the initial form of treatment. The avoidance of surgery with preservation of ejaculatory function in 78% of Stage IIA and IIB patients argues in favour, of an initially non-surgical approach to management.     

Enhanced metastasis after local therapy in a murine model using C-1300 neuroblastoma

BACKGROUND/PURPOSE: In the treatment of advanced neuroblastoma, the role of surgery has been controversial. This study was carried out to determine the effect of surgery, irradiation, and chemotherapy in inhibiting or promoting distant metastases. METHODS: Transplanted C-1300 neuroblastomas in hind legs of syngeneic mice were treated by surgery, radiation, and chemotherapy. The liver was evaluated 18 days after each treatment modality for metastases. RESULTS: Mice developed no liver metastasis when leg tumors received no treatment or chemotherapy. In the mice who had the tumor resected, liver metastases were found in 8 of 16 mice that had 7-mm tumors. One hundred percent of the mice that had 9- or 12-mm tumors presented with metastases to the liver. In mice who received radiation therapy, 100% had liver metastases. CONCLUSIONS: Local control by surgery and single-dose radiation induced liver metastasis in a murine model. Surgery to remove tumors should be used in conjunction with chemotherapy to prevent secondary liver metastases.     

Cytoreductive surgery and HIPEC in peritoneal recurrent ovarian cancer: experience and lessons learned

Purpose

Peritoneal recurrence of ovarian cancer is frequent after primary surgery and chemotherapy and has poor long-term survival. De novo cytoreductive surgery is crucial with the potential to improve prognosis, especially when combined with hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

The sampled data of 40 consecutive patients were retrospectively analyzed. Thirty-one patients were treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy.

Results

No patient was lost in the perioperative period, and the combined procedure was performed with acceptable morbidity. Colon-preserving cytoreductive surgery was associated with reduced morbidity.

Conclusions

Patients suffering from peritoneal recurrence of ovarian cancer should be considered for radical reoperation with HIPEC in a center with expertise in multimodal therapeutic options. Organ-preserving cytoreductive surgery allows complete cytoreduction with the goal of decreasing morbidity.     

Germ cell testicular tumours with lung metastases: Chemotherapy and surgical treatment

Eighty patients with stage IV testicular germ cell tumours with lung metastases were treated with PVB chemotherapy and subsequent surgery in cases of residual disease. Out of 80 patients 28 (35%) achieved complete response following chemotherapy alone. Thirty-six patients (45%) with partial response underwent surgery: 17 had lymphadenectomy because of residual mass in the retroperitoneum, 15 had pulmonary surgery alone and 4 had both operations. Of these 36 patients 27 achieved complete response following cytostatic and surgical treatment. Sixteen patients died following PVB chemotherapy, 10 of them due to progression of disease, and there were six (7.5%) drug-related deaths. The authors refer to the importance of surgical treatment of residual metastatic mass in the lungs following PVB chemotherapy. Germ cell tumours of the testis are the most curable solid neoplasms treated by the oncologist. Advances in their management are due to the introduction of cisplatin-based combination chemotherapy and surgical removal of the residual mass [8]. Progress in chemotherapy of testicular tumours has changed the attitude towards thoracotomy and surgical removal of lung metastases. The aim of this study is to evaluate combined cytostatic and surgical treatment of disseminated testicular tumours with emphasis on surgical removal of residual lung metastases following chemotherapy.     

Malignant gliomas treated after surgery by combination chemotherapy and delayed irradiation

Summary Forty-six patients with gliomas were introduced after surgery into a therapeutic programme of six cycles of combination chemotherapy with VM₂₆ and CCNU, followed by delayed irradiation six months after surgery with an average dose of 5,800 rads. After irradiation the same preradiation chemotherapy was readministered for an average of four cycles. The results were compared to those from another group of 28 patients treated only by the same chemotherapy (CRC and C groups successively).Twelve patients (26%) died before irradiation in the CRC group, six patients (13%) had recurrences at the time of irradiation, and 28 patients (61%) had no clinical or radiological signs of recurrence at the time of irradiation. For the total of treated patients the median survival after surgery was 17 months, and 46% of the patients were surviving at 18 months. The percentage of survivors at 18 months was significantly more elevated in the group treated by combination chemotherapy and delayed irradiation than in a control group treated by the same combination chemotherapy alone. This result suggests that in approximately 50% of cases combination chemotherapy after surgery, and delayed irradiation six months after surgery, cumulated their effects on survival time.     

Mediastinal germ cell tumors

Mediastinal germ cell tumors are uncommon tumors that occur predominantly within the anterior mediastinum and frequently present as a very large mass with local compression. Symptoms are typically vague and represent the local mass effects of the tumor. Chest computed tomography and examination of serum tumor markers provide the critical workup before a tissue diagnosis is obtained. Seminomas are extremely sensitive to both chemotherapy and radiation and are primarily treated nonsurgically. Benign teratomas without malignant elements are extremely resistant to both chemotherapy and radiation and are treated exclusively with surgical resection with excellent outcomes. Malignant nonseminomatous germ cell tumors are primarily treated with chemotherapy, with adjuvant surgery reserved for patients with residual mediastinal masses after systemic therapy.     

Use of an Implantable Catheter System for Intraperitoneal Chemotherapy in Ovarian Cancer

Abstract: To check the efficiency of intraperitoneal chemotherapy of ovarian carcinomas, 15 patients were treated with instillations of mitoxantrone or cisplatinum. An implantable catheter system was used to access the abdominal cavity. Local therapy proved to be without any effect when large tumor masses were treated. Patients with small tumor residues after surgery did not benefit either, partly because of extraperitoneal progress of the disease. Patients without evidence of disease proved to be stable. Side effects of the therapy were usually mild compared with those of systemic chemotherapy. Access to the peritoneal cavity with the implantable catheter proved to be safe and reliable.