A phase II trial of chemotherapy and surgery for non-small cell lung cancer patients with a synchronous solitary metastasis

PURPOSE: Retrospective reports suggest that selected patients with non-small cell lung cancer (NSCLC) and a solitary synchronous site of M(1) disease may be effectively treated by resection of all disease sites. The feasibility and potential benefit of combining surgery and chemotherapy in this setting are unclear. Therefore, we performed a prospective trial to test this therapeutic approach. METHODS: Patients with solitary synchronous M(1) NSCLC with or without N(2) disease were to receive three cycles of mitomycin, vinblastine, cisplatin (MVP) chemotherapy, followed by resection of all disease sites, and then two cycles of VP chemotherapy. Solitary brain metastases were to be resected before chemotherapy. RESULTS: From 10/92-2/99, 23 patients (12 men, 11 women, median age = 55 years) were enrolled. Mediastinoscopy, performed in 22 patients, showed involved N(2) nodes in 12. The M(1) sites included brain (14 patients) adrenal (3), bone (3), spleen (1), lung (1), and colon (1). Of 12 patients who completed all three induction therapy cycles, 8 underwent R(0) resections. Another 5 patients had R(0) resections without completing induction therapy. Eight of the 13 patients undergoing R(0) resections completed postoperative chemotherapy. The median survival was 11 months; 2 patients survived to 5 years without disease. CONCLUSIONS: (1) The number of patients with solitary M(1) disease who qualified for this combined modality therapy was small; (2) MVP was poorly tolerated as induction chemotherapy in this patient population; (3) Compared to historical experience with surgery alone, overall survival does not appear to be superior with this treatment strategy.     

Prognosis in Renal Cell Carcinoma: Analysis of Clinical Course following Nephrectomy

The clinical courses and survivals of 159 patients who underwentnephrectomy for renal cell carcinoma are reviewed. A longerdiseae-free period after nephrectomy was correlated with significantlybetter survival. Among patients in whom metastases in the lungsor bones were detected after nephrectomy, those with betweenone and five pulmonary or solitary bone metastases, wihtoutdefinite increases in their number and size in the six monthsfollowing their first appearance, survived significantly longerthan patients with a similar number of metastases but whichdid increase in number and size in the following six months,or patients with six or more pulmonary or multiple bone metastases.Even when metastases detected after nephrectomy were confinedto the lungs or bones throughout the observation period, thepatients did not necessarily show significantly better survivalsthan patients with metastases detected in multiple sites.     

Surgical resection of hepatic metastasis from gastric cancer: a review and new recommendation in the Japanese gastric cancer treatment guidelines

Liver metastases from gastric cancer are rarely indicated for surgery because they are often diagnosed as multiple nodules occupying both lobes and coexist with extrahepatic disease. A literature search identified no clinical trials on hepatectomy for this disease; only retrospective studies of a relatively small number of cases collected over more than a decade, mostly from a single institution, were found. Five-year survival rates from these reports ranged from 0 % to 37 %, and long-term survivors were observed among carefully selected case series. The most commonly reported prognostic factor was the number of metastatic nodules, and patients with a solitary metastasis tended to have superior outcome. Patients diagnosed to have a small number of metastatic nodules by modern imaging tools could be indicated for surgery. Because both intrahepatic and extrahepatic recurrences are common, patients are likely to benefit from perioperative adjuvant chemotherapy, although it is not possible at this time to specify which regimen is the most appropriate.     

A long-term follow-up and management study of hepatocellular carcinoma patients surviving for 10 years or longer after curative hepatectomy

BACKGROUND: The aims of the current study were to elucidate the clinicopathologic characteristics and disease recurrence patterns of patients with hepatocellular carcinoma (HCC) who survived for 10 years or longer after undergoing an initial hepatectomy. METHODS: Between January 1987 and December 1993, 578 patients underwent potentially curative hepatectomy at the study institution. Disease recurrence and follow-up data were available for 481 of these patients, who then were followed for more than 10 years after the initial hepatectomy. Fourteen clinicopathologic features were compared between the 10-year survivors and those patients who died within 10 years after the surgery. The risk factors for disease recurrence, the recurrence status, time to recurrence, and treatment modalities for recurrence were examined among the 10-year survivors. RESULTS: There were 105 10-year survivors (21.8%), including 42 disease-free survivors (8.7%). Favorable independent factors found to be correlated with 10-year survival were age < 55 years, a plasma retention rate of indocyanine green at 15 minutes of < 15%, the presence of a solitary tumor, the absence of intrahepatic metastases, the absence of portal vein invasion, and the absence of underlying cirrhosis. A negative test for the the hepatitis C antibody and the absence of intrahepatic metastases were found to be independent predictive factors for 10-year disease-free survival among the 10-year survivors. CONCLUSIONS: The results suggest that younger patients without underlying cirrhosis who have a solitary HCC that does not demonstrate vascular invasion might survive for longer than 10 years after the initial hepatectomy. In addition to close surveillance in such patients after hepatectomy, repeat hepatectomy, local ablation therapy, and transhepatic arterial chemoembolization may contribute to long-term survival, even if disease recurrence occurs.     

A solitary functioning osseous metastasis from a malignant pheochromocytoma of the organ of Zuckerkandl

A case of a malignant phenochromocytoma of the organ of Zuckerkandl is reported. There was a solitary functional metastasis in the left femur, which was treated by hip disarticulation after removal of the primary. The patient is asymptomatic and free of further metastases after 3 years. Other reported cases of solitary metastases from malignant pheochromocytomas are cited. These occurred most frequently in the skeleton system, which is the most common site of distant metastases in malignant pheochromocytoma. The reported case and the review of the literature indicate that solitary or limited metastatic lesions should be treated surgically by partial or, when possible, complete resection.     

Brain metastases with an unknown primary: a clinical perspective

A review of 43 patients with cerebral metastases, an unknown primary, and no other sites of metastases is presented. 27/43 (62.7%) had solitary metastases and 37.2% (16/43) had multiple metastases. Surgical treatment involved complete resection in 30.2%, subtotal resection in 37.2% and biopsy alone or no surgical procedure in the remainder. 39/43 patients underwent whole brain irradiation with the majority receiving 3000–4000 rads/10–20 fractions. Overall survival was 52% at six months and 20% at one year, and was significantly better in patients with solitary as opposed to multiple metastases (p < 0.03). A failure analysis including autopsy data demonstrates that (28/41) 68.3% of patients died of progressive intracranial disease without extracerebral metastases. Implications for treatment strategies are discussed.     

Brain metastases from epithelial ovarian cancer: a review of the literature

BACKGROUND: Brain metastases from epithelial ovarian cancer (EOC) are rare. This report is based on a review of the literature. METHODS AND RESULTS: This review summarizes the incidence, clinical features, pathophysiology, and diagnostic evaluation of EOC. The section on current treatment includes a thorough evaluation of the literature, highlights controversies over treatment options, and provides insight into novel approaches. Current treatment options include surgical resection, whole-brain radiation therapy (WBRT), stereotactic radiosurgery, and chemotherapy. Corticosteroids and anticonvulsant medications are commonly used for the palliation of mass effects and seizures, respectively. In the reviewed series, a better outcome was seen following surgical resection and WBRT with or without chemotherapy for solitary and resectable brain metastases. CONCLUSION: The prognosis for patients with brain metastases from EOC is poor. A better outcome might be obtained using multimodality therapy. Because of the small number of patients included in the reported studies, multicenter clinical trials are needed for further investigation in order to critically evaluate the clear benefit of these treatment options in selected patients.     

Distant metastases of malignant thyroid cancer. A retrospective study of 892 cases

In 892 patients with thyroid carcinoma, distant metastases developed in 151 cases, and these were classified according to conventional pathohistological types and--in particular--to the incidence of surgically treatable solitary sites. The aim of the present study was also to investigate whether the histological diagnosis is of value in predicting the pattern of metastatic spread. Distant metastases of anaplastic carcinoma and sarcoma were found most frequently in the lungs (70 out of 81 patients, this is 86%), with 4 cases being solitary tumors. Metastatic spread into the skeleton, however, occurred rarely (14 out of 81 patients, 17.3%), when compared with differentiated carcinoma (64.8%). Moreover, with the exception of 1 case, metastatic growth was not solitary but involved more areas in bone. On the other hand, the well differentiated carcinoma displayed a greater predilection for the metastatic spread to the skeleton: 35 cases of bone involvement were identified in 54 patients with distant metastases (64.8%), and out of these cases, 10 metastases were solitary. Metastatic spread into the lungs occurred less often (30 of the 54 patients, 55.5%) and always displayed a diffuse pattern or involved multiple sites. In some cases, solitary metastases of different histological types were also identified in other organs. Our findings suggest that the pathohistological classification appears to be of use in guiding the clinical approach to a curative extirpation of distant solitary metastases in selected patients.     

A review of stereotactic radiosurgery in the management of brain metastases

This review addresses the epidemiology, historical reports, current issues, data and controversies involved in the management of brain metastases. The literature regarding surgery, whole brain radiation therapy, stereotactic radiosurgery or some combination of those treatments is discussed as well as issues of cost-effectiveness. Ongoing prospective randomized trials will further elucidate the optimal management for patients with brain metastases. Until those data are available, clinicians are encouraged to apply the existing data reviewed here in conjunction with best clinical judgment. A brief clinical guide is as follows. Patients with a solitary metastasis in an operable location and symptomatic mass effect should undergo surgery. Patients with poor performance status (KPS < 70) or more than three brain metastases should receive WBRT alone. Patients with 1-3 brain metastases and KPS >or= 70, should receive WBRT + SRS. If the patient refuses WBRT or needs salvage after WBRT, then SRS alone is appropriate. Clinicians should not be too dogmatic and should always apply the best clinical judgment.     

可切除结直肠癌肺转移的预后因素分析

目的 探讨结直肠癌肺转移根治性切除术后的预后影响因素.方法 回顾性分析行根治性切除术的60例结直肠癌肺转移患者的临床资料.结果 全组患者肺转移瘤切除术后和结直肠癌切除术后的5年生存率分别为43.7%和74.0%.单因素分析结果显示,肺转移瘤数目和无瘤间期与结直肠癌术后患者的总生存率有关(均P＜0.05),肺转移瘤切除前癌胚抗原(CEA)水平、肺转移瘸数目、有无肺门和纵隔淋巴结转移与肺转移瘤切除术后患者的生存率有关(均P＜0.05).多因素分析结果显示,肺转移瘤数目和无瘤间期是结直肠癌术后患者预后的独立影响因素(OR=2.691,95% CI为1.072～6.754;OR=0.979,95% CI为0.963～0.994),肺转移瘤数目、有无肺门和纵隔淋巴结转移是肺转移瘤切除术后患者预后的独立影响因素(OR=3.319,95% CI为1.274～8.648;OR=3.414,95% CI为1.340～8.695).结论 经过严格选择的结直肠癌肺转移患者,尤其是单发肺转移及无肺门和纵隔淋巴结转移的患者,行根治性切除术后可获得长期生存.     

Number of metastatic sites is a strong predictor of survival in patients with nonsmall cell lung cancer with or without brain metastases

BACKGROUND:

The staging system for non–small cell lung cancer (NSCLC) does not consider tumor burden or number of metastatic sites, although oligometastases are more favorable.

METHODS:

Using log‐rank testing, the authors analyzed overall survival (OS) in 1284 patients newly presenting with metastatic NSCLC by number of metastatic organ sites and the presence of brain metastases.

RESULTS:

OS for patients without brain metastases was found to be correlated with the number of metastatic sites (P = .0009). Brain metastases conferred an inferior OS (median of 7 months vs 9 months; 95% confidence interval, 7‐8 months vs 8‐10 months [P = .00,002]). To evaluate the influence of tumor burden on OS, the authors considered subsets of patients in whom the brain (n = 135) or lung (n = 137) was the solitary metastatic organ site. In patients with brain metastases, OS was found to be correlated inversely with the volume of all metastases or the largest lesion (hazards ratio, 1.04 or 1.03, respectively; P = .01). For patients with lung metastases, OS was better for those with a maximum tumor size below the median of 40 mm (P = .0004).

CONCLUSIONS:

Staging of NSCLC and clinical trial patient stratification should include quantitation of tumor burden. The prognostic impact of brain metastases is small and partly dependent on tumor volume, which indicates the need for aggressive therapy for patients with NSCLC brain metastasis and their inclusion in clinical trials. Cancer 2009. © 2009 American Cancer Society.     

Pseudo-chondrosarcoma: solitary osseous metastases from atypical bronchogenic carcinoma.

A patient with bronchogenic carcinoma with a solitary metastases to the femur in whom the clinical, radiologic, and pathologic setting suggested that the primary tumor was the bone lesion (chondrosarcoma) and the pulmonary lesion was a solitary metastasis is presented. This case is added to the limited literature indicating that mucin-secreting tumors metastatic to bone may simulate primary bone tumors radiographically.     

非小细胞肺癌孤立性骨转移的治疗

非小细胞肺癌（NSCLC）骨转移的治疗方法有手术、化疗、放疗等。近年来分子靶向治疗如地诺单抗成为NSCLC骨转移新的治疗方法。尽管治疗手段众多,但是NSCLC骨转移患者预后仍未得到明显改善。对于孤立性骨转移患者,积极的治疗可改善患者的生存及预后。     

Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.     

Alveolar rhabdomyosarcoma of the female genitalia

Eight cases of alveolar rhabdomyosarcoma of the female genitalia were diagnosed from 1963 to 1983 at The University of Texas M. D. Anderson Hospital. The primary sites were vulva in two, perineum in five, and broad ligament in one patient. When possible, therapy was initiated with local tumor excision (five patients). Surgery was followed by local or regional radiation (six patients) and chemotherapy (seven patients). Of the eight patients, five died within 9 months, one died 27 months after diagnosis, and only two are 5-year survivors. The aggressive behavior of this tumor is evidenced by autopsy findings of widespread metastases. Metastatic disease to the bone was present in four patients and to the breast in three patients. Local disease was controlled in two patients who died of distant metastases. Current therapy recommendations include excisional surgery, local radiation, and combination chemotherapy. A need for more effective chemotherapeutic programs is evident.     

Squamous carcinoma arising in a pilonidal sinus

A patient with squamous cell carcinoma arising from an extensive pilonidal sinus was treated with wide local excision, resulting in an apparent cure over a 1-year follow-up period. Review of the literature revealed 32 previously reported cases of this entity. Forty-four percent of these patients developed recurrences or metastases, and 22% died of their disease. The largest historical treatment group with at least 1-year follow-up (19 patients with localized disease) underwent wide excision. Forty-two percent of these patients recurred or developed metastases. Ultimately, 89.5% of these patients were reported cured, but only five survivors were followed for as long as 5 years. Historical experience appears to identify pilonidal tract squamous carcinoma as an aggressive tumor. The reported success of wide local excision is based on a small number of patients followed for short periods of time. Continued experience with this disease should be reported to verify the adequacy of local excision or identify the need for adjunctive therapy.     

Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis

BACKGROUND: Solitary brain metastases occur in about 50% of patients with brain metastases from nonsmall cell lung cancer (NSCLC). The standard of care is surgical resection of solitary brain metastases, or stereotactic radiosurgery (SRS) plus whole brain radiation therapy (WBRT). However, the optimal treatment for the primary site of newly diagnosed NSCLC with a solitary brain metastasis is not well defined. The goal was to distinguish which patients might benefit from aggressive treatment of their lung primary in patients whose solitary brain metastasis was treated with surgery or SRS. METHODS: The cases of 84 newly diagnosed NSCLC patients presenting with a solitary brain metastasis and treated from December 1993 through June 2004 were retrospectively reviewed at The University of Texas M. D. Anderson Cancer Center. All patients had undergone either craniotomy (n = 53) or SRS (n = 31) for management of the solitary brain metastasis. Forty-four patients received treatment of their primary lung cancer using thoracic radiation therapy (median dose 45 Gy; n = 8), chemotherapy (n = 23), or both (n = 13). RESULTS: The median Karnofsky performance status score was 80 (range, 60-100). Excluding the presence of the brain metastasis, 12 patients had AJCC Stage I primary cancer, 27 had Stage II disease, and 45 had Stage III disease. The median follow-up was 9.7 months (range, 1-86 months). The 1-, 2-, 3-, and 5-year overall survival rates from time of lung cancer diagnosis were 49.8%, 16.3%, 12.7%, and 7.6%, respectively. The median survival times for patients by thoracic stage (I, II, and III) were 25.6, 9.5, and 9.9 months, respectively (P = .006). CONCLUSIONS: By applying American Joint Committee on Cancer staging to only the primary site, the thoracic Stage I patients in our study with solitary brain metastases had a more favorable outcome than would be expected and was comparable to Stage I NSCLC without brain metastases. Aggressive treatment to the lung may be justified for newly diagnosed thoracic Stage I NSCLC patients with a solitary brain metastasis, but not for locally advanced NSCLC patients with a solitary brain metastasis.     

Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skull

PURPOSE: To evaluate the efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) using noninvasive fixation of the skull on solitary or oligo brain metastatic patients as an alternative to stereotactic radiosurgery (SRS) using invasive fixation. PATIENTS AND METHODS: The subjects were 87 patients who had 4 or fewer brain metastases (50 solitary, 37 oligometastases). Treatment was conducted on 159 metastases by using a linac-based stereotactic system. The median isocentric dose was 35 Gy in 4 fractions. Whole-brain irradiation was not applied as an initial treatment. For the salvage treatment of metachronous brain metastases, repeat HSRT or whole-brain irradiation was applied. RESULTS: The actuarial 1-year local tumor control rate was 81%. Treatment-related complications were observed in 4 patients in the early period (<3 months) and in 2 patients in the late period. The median survival period was 8.7 months. Metachronous brain metastases occurred in 30 patients, and none of the 18 patients who were eligible for salvage HSRT refused to receive it again. CONCLUSIONS: Hypofractionated stereotactic radiotherapy achieved tumor control and survival equivalent to those of SRS reported in the literature. The results suggested that HSRT could be an alternative for solitary or oligo brain metastatic patients with less toxicity and less invasiveness compared to SRS.     

Isolated brain metastases as first site of recurrence in prostate cancer: case report and review of the literature

Fewer than 2% of patients with metastatic prostate cancer (pca) develop brain metastases. Autopsy series have confirmed the rarity of brain metastases. When present, brain metastases occur in end stage, once the pca is castrate-resistant and spread to other sites is extensive. Here, we present a rare case of a patient with pca who developed a solitary parenchymal brain metastasis as first site of relapse 9 years after radical therapy. The patient underwent craniotomy and excision of the tumour. A second recurrence was also isolated to the brain. In the literature, pca patients with brain metastases have a poor mean survival of 1–7.6 months. The patient in our case report experienced a relatively favourable outcome, surviving 19 months after his initial brain relapse.     

Sémiologie des métastases osseuses en radiologie conventionnelle

Bone metastases are detected at initial diagnosis of cancer in 25% of cases and bone metastases are common in the course of a majority of cancer types. The spine and proximal long bones are the most affected sites. Knowledge of the basic radiological semiology is important to make the proper diagnosis of metastasis(s) bone(s), especially in situations in which the clinical context is not suggestive of metastases (such as cases where bone metastases are inaugural or cases of peripheral solitary metastasis). Tumor aggressiveness can be assessed at the level of the cortical bone and periosteum. Lodwick criteria are useful for the diagnosis of malignancy and tumor aggressiveness at initial diagnosis on plain radiographs, which are very important in the context of bone metastases. A CT scanner is required to confirm the malignancy of a bone lesion. MRI is complementary to the scanner including for the assessment of bone marrow involvement and tumor extensions.