Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89.

PURPOSE: To evaluate a multimodal approach including surgery and cisplatinum chemotherapy for treatment of children with malignant sacrococcygeal germ cell tumors (GCT) and to compare adjuvant and neoadjuvant strategies in advanced tumors. PATIENTS AND METHODS: Between 1983 and 1995, 71 patients with malignant sacrococcygeal GCT were prospectively enrolled onto the German protocols for nontesticular GCT Maligne Keimzelltumoren 83/86 and 89. Five patients who received no chemotherapy (n = 2) or nonplatinum chemotherapy (n = 2) or who did not undergo tumor resection (n = 1) were excluded from this analysis. Among the 66 patients analyzed were 14 boys and 52 girls. The median age was 17.4 months (range, 7 months to 119 months). Median follow-up was 79 months (range, 4 months to 145 months). RESULTS: Fifty-two patients presented with locally advanced stage T2 tumors, and 30 patients had distant metastases at diagnosis. Patients received a median of eight cycles (range, four to nine cycles) of cisplatinum-based chemotherapy. Thirty-five patients underwent tumor resection at diagnosis and received adjuvant cisplatinum-based chemotherapy (group A). Thirty-one patients received up-front chemotherapy followed by delayed tumor resection (group B). Group B included more metastatic tumors than group A (group B, 19 of 31 patients; group A, 11 of 35 patients, P =.01). Preoperative chemotherapy facilitated complete tumor resections (group B, 20 of 31 patients; group A, five of 35 patients, P <.001) and avoided second-look surgery. Metastases at diagnosis and completeness of the first attempt of tumor resection were significant prognostic predictors; however, metastases were not predictive for patients treated with up-front chemotherapy. At 5 years follow-up, event-free survival was 0.76 +/- 0.05 (50 of 66 patients), and overall survival was 0.81 +/- 0.05 (54 of 66 patients). Four patients died as a result of therapy-related complications, and eight patients died of their tumors. Patients with locally advanced and metastatic tumors (T2b M1) fared better with neoadjuvant treatment [overall survival: 0.83 +/- 0.09 (16 of 19 patients) versus 0.45 +/- 0.15 (five of 11 patients), P =.01]. CONCLUSION: Even locally advanced and metastatic sacrococcygeal GCT can be successfully treated with up-front cisplatinum-based chemotherapy followed by delayed but complete tumor resection.     

Preoperative treatment of advanced skin carcinoma with cisplatin and bleomycin

In advanced skin carcinomas of the head and neck region, the tumor may be unresectable or curative resection or radiation may either fail or produce poor functional and cosmetic results. The goal of this study was to test the ability of preoperative chemotherapy to decrease the extent of needed resection and tumor response. Five patients, three with squamous cell carcinoma and two with basal cell carcinoma, were treated before surgery with three cycles of cisplatin 20 mg/m2 daily for 4 days and bleomycin 20 mg/day for 4 days by continuous infusion every 3 weeks. All patients had advanced cancer in the head and neck region, one had unresectable tumor, two had xeroderma pigmentosum, and one was a 13-year-old child. The history of prior treatments was as follows: radiation therapy (n = 3), systemic chemotherapy (n = 1), surgery (n = 1), and no treatment (n = 1). One patient had complete clinical but not pathologic response, three had partial response, and one had progressive disease. The extent of resection after chemotherapy was dramatically reduced in the patient with a complete response and minimally changed in the patients with partials responses and progressive disease. All patients who underwent surgery became tumor free. Preventable toxicity was symptomatic hypomagnesemia in one patient, reversible elevation of creatinine in one patient, and mild nausea and vomiting in three patients. With this report, the total number of patients with nonmelanoma skin cancer who were treated with cisplatin is 68, and their overall response is 80%. Only 16 reported patients were treated with preoperative chemotherapy, and study of this treatment approach to advanced skin cancer should be pursued.     

Les tumeurs neuroectodermiques mélanotiques infantiles : état actuel des connaissances

Melanotic Neuroectodermal Tumors of Infancy (MNTI), also known as melanotic progonoma are rare tumors affecting young children. The main locations are primarily head, neck and cranial vault. Complete surgical resection remains the standard treatment for these tumors leading to healing in the majority of cases. However, recurrent, metastatic or locally advanced forms require other treatments. The literature since 1980 reported 27 cases of patients who received treatment with chemotherapy and/or radiation therapy. Among the 24 patients who received chemotherapy, a reduction or stabilization of tumor volume was observed in 14 observations. Nine patients received radiation therapy and one patient experiences a tumor improvement. The information provided by this review can evoke the chemosensitivity of this rare tumor type but are insufficient to conclude about their radiosensitivity.     

68例骨肿瘤致病理性骨折的治疗

目的:研究不同的外科治疗方法对骨肿瘤病理性骨折患者预后的影响.方法:自1995年6月～2002年10月共收治68例病理性骨折.引起病理性骨折的肿瘤中,转移癌27例(转移至四肢17例,脊柱8例,锁骨2例).原发恶性肿瘤20例(骨肉瘤13例,尤文氏肉瘤3例,软骨肉瘤2例,恶性纤维组织细胞瘤2例).良性肿瘤21例(骨巨细胞瘤12例,骨囊肿4例,内生软骨瘤及动脉瘤样骨囊肿各2例,纤维异样增殖症1例).通过回顾性分析研究,对其临床表现、诊断、治疗进行初步临床分析.结果:随访6个月～7.2年,转移癌中7例行局部广泛切除,假体置换,未见局部复发,功能良好.8例行病灶刮除,髓内针内固定,其中4例死亡,3例局部复发.13例骨肉瘤患者,9例对化疗敏感,行保肢手术,术后未见局部复发,预后良好,4例对化疗不敏感,行截肢术,术后均有肺转移.12例骨巨细胞瘤,7例行肿瘤广泛切除,假体置换,术后随访未见局部复发.5例行病灶刮除,骨水泥填充,其中3例复发.结论:对于转移癌、骨巨细胞瘤和一些良性肿瘤所致的病理性骨折,肿瘤的彻底切除和假体置换对于控制局部复发是有效的,并可获得良好的功能.对化疗敏感的骨肉瘤患者,即使骨折,经过化疗和适当处理后,也可行肿瘤的彻底切除和假体置换,也可获得良好的局部控制和降低肺转移发生率.     

Docetaxel and cisplatin: An active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck

Background: Docetaxel and cisplatin are among the most active antitumor agents in head and neck cancer, and phase I studies found the combination of the two drugs to be feasible. The EORTC ECSG performed a multicenter phase II study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck to evaluate the antitumor efficacy and toxicity of this combination.Patients and methods: Eligibility criteria included written informed consent, a WHO performance status <2, life expectancy of >12 weeks, and adequate bone marrow, liver and renal function. Neoadjuvant pretreatment with cisplatin-based chemotherapy or prior radiotherapy were allowed. Patients were ineligible if pretreated with taxoids, had CNS involvement, concurrent malignancy, peripheral neuropathy, or no measurable disease. Treatment consisted of docetaxel 100 mg/m2 (one-hour i.v. infusion), followed by cisplatin 75 mg/m2 (three-hour i.v. infusion), repeated every three weeks. Supportive care included hydration, 5HT3- antagonists, and corticosteroids.Results: Forty-four patients (median age 55 years, range 35–76) entered the trial; 41 patients were eligible, 164 cycles of treatment were evaluable for toxicity, and 31 patients for response. Fourteen patients had undergone prior surgery, 15 had received radiotherapy, and five had had chemotherapy. A median number of four treatment cycles (range 1–6) was given. Hematologic and non-hematologic toxicities were common, but hypersensitivity reactions and fluid retention were very infrequent due to corticosteroid prophylaxis. Four patients were taken off the study due to toxicity, and one toxic death occurred due to pneumonia. Among 41 eligible patients, objective responses as confirmed by independent review included six complete remissions and 16 partial remissions, resulting in an overall response rate of 53.7% (95% confidence interval: 37.4%–69.3%). Responses occurred in locally advanced, recurrent and metastatic disease, both in pre- and non-pretreated patients. Of 22 evaluable, non-pretreated patients with locally advanced or metastatic disease, five achieved complete responses, and 14 partial responses. Observed among nine evaluable pretreated patients with locally advanced or metastatic head and neck cancer were one complete response and two partial responses.Conclusion: The combination of docetaxel and cisplatin is feasible and active in locally advanced, recurrent, and metastatic squamous cell carcinoma of the head and neck.     

Neoadjuvant chemotherapy followed by surgery in lung cancer: Indian scenario

A vast majority of the patients with lung cancer in India present as advanced stage disease and a significant number among them have nonmetastatic locally advanced tumors which require multimodality management with curative intent. We analyzed the treatment outcome of the patients treated with of neoadjuvant chemotherapy followed by surgery approach. This was a retrospective analysis of institutional database of all non–small cell lung cancer patients who underwent neoadjuvant chemotherapy followed by curative intent surgery with/without adjuvant therapy from 2012 to 2018. Patients included were those with N2 disease; T4 or T3 disease requiring pneumonectomy or extensive adjacent structures resection. Mediastinal staging was done by PET-CT (Positron Emission Tomography - Computed Tomography) along with Endobronchial ultrasound in most cases. All the patients received platinum-based doublet chemotherapy for 3-6 cycles before surgery. Response to neoadjuvant chemotherapy and survival were analyzed. A total of 44 patients fulfilled the eligibility criteria. Majority were males (81.8%) and smokers (75%). Squamous cell carcinoma (50%) was the most common subtype. Total 43.2% patients had either T3 or T4 tumors. N2 disease (either single station or multistation) was observed in 67.2% cases. A complete pathologic response was observed in 22.7% cases. In addition, 6.8% patients had ≤10% viable tumor in the resected specimen. Residual disease in N2 nodes were found in 25% cases. Median follow-up was 35.9 months. Patients with residual N2 disease showed a trend toward inferior survival. In multivariate analysis smoking, pretreatment tumor category and final pathologic stage were significant factors for disease free but not for overall survival. This study shows that neoadjuvant chemotherapy is a feasible and effective modality for downstaging locally advanced cases of non–small cell lung cancer among the Indian patients. Patients with less than 10% residual tumor burden had a better survival. The role of surgery in those with persistently N2 needs further evaluation.     

Treatment of refractory metastatic choriocarcinoma with tandem high-dose chemotherapy supported by peripheral blood stem cell transplantation: A case report

Currently, 70% to 80% of patients with advanced germ cell tumors can be cured with cisplatin-based chemotherapy, followed by surgical resection of the residual tumor. The prognosis, however, is uniformly poor for patients who fail to respond to induction chemotherapy. In this report, we describe a patient with retroperitoneal choriocarcinoma and multiple lung metastases, who was refractory to cisplatin-based chemotherapy, but who achieved a durable marker-negative partial response after 2 cycles of high-dose chemotherapy, supported by autologous, peripheral blood stem cell transplantation. The patient is now alive and well, without recurrence, more than 24 months after this therapy.     

Upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer with synchronous liver metastases

BackgroundThe optimal treatment of locally advanced rectal cancer with synchronous liver metastases remains controversial. In this study, we aimed to evaluate the safety, efficacy, and oncologic outcomes of upfront chemotherapy and short-course radiotherapy with delayed surgery in patients with locally advanced rectal cancer and synchronous liver metastases.MethodsForty-four patients who underwent upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer (cT3/4, <2.0 mm from the mesorectal fascia) with synchronous liver metastases between January 2010 and June 2017 were reviewed retrospectively. Primary and metastatic liver lesions were resected with curative intent. Upfront chemotherapy and short-course radiotherapy were administered. Thereafter, restaging, surgery only, or additional chemotherapy followed by surgery was performed.ResultsAt the time of initial diagnosis, 20 patients had <3 liver metastases; 24 patients had ≥3 liver metastases. Twenty-three patients had hemi-liver metastases; 21 patients had bilobar liver metastases. R0 resection of rectal lesions was achieved in 43 patients. Synchronous R0 resection of liver metastases was achieved in 41 patients. Postoperative complications (Clavien–Dindo Grade ≥ III) were noted in 5 patients. Grade 3/4 adverse events were observed in 26 patients. All adverse events were managed effectively with medication and supportive care. The 3-year overall survival and progression-free survival rates were 65.3% and 26.9%, respectively.ConclusionUpfront chemotherapy and short-course radiotherapy with delayed surgery appear to be safe and effective in patients with locally advanced rectal cancer and synchronous liver metastases without substantially increasing treatment induced morbidity.     

Surgical resection of solitary metastases after chemotherapy in patients with nonseminomatous germ cell tumors and elevated serum tumor markers.

BACKGROUND. Chemorefractory metastatic germ cell tumors and elevated tumor markers generally indicate inoperable disease. METHODS. Solitary metastases were resected in 15 patients who had a nonseminomatous germ cell tumor and an elevated alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG) serum level after treatment with cisplatin-based chemotherapy. Patients underwent resection for a residual mass after chemotherapy or for a new solitary metastasis after achieving a complete response (CR) to salvage chemotherapy. RESULTS. Seven patients were disease-free after surgical resection alone. All five patients with an elevated HCG level had a relapse after surgery compared with 3 of 10 patients with only an elevated AFP level. Only 4 of 10 patients with a retroperitoneal metastasis had a relapse after surgery compared with 4 of 5 patients with visceral disease. Eleven of 15 patients overall were disease-free after surgery and subsequent chemotherapy after a relapse. CONCLUSIONS. Surgical resection of a solitary metastasis despite elevated serum tumor markers should be considered in patients who have not had a durable CR to cisplatin-based chemotherapy.     

First-line systemic treatment with gefitinib in stage IV non-small cell lung cancer

Lung cancer has a high mortality rate and is often diagnosed in locally advanced or metastatic stages. A new therapeutic option for patients with non-small cell lung cancer (NSCLC) in these stages with progress or relapse after platinum-based chemotherapy exists in the inhibitors of the epidermal growth factor receptor (EGFR) tyrosine-kinase. EGFR tyrosine-kinase inhibitor treatment might also be an option for patients ineligible for surgery and conventional chemotherapy. We present a case of a 53-year-old woman who was diagnosed due to pain from multiple bone metastases of a lung adenocarcinoma. She refused cytotoxic chemotherapy, and we administered first-line systemic treatment with gefitinib subsequent to radiotherapy of metastatic bone disease. The patient responded well to gefitinib treatment and achieved a partial response after 3 weeks. No relevant side effects occurred, and the patient experienced an 8-month remission of disease. With a follow-up of 10 months, the patient is still alive. Retrospectively, we found a mutation of the EGF receptor in tumor cells of the patient, which is associated with sensitivity to gefitinib. EGFR tyrosine-kinase inhibitors (TKI) can be an alternative first-line systemic treatment option for selected patients with metastatic NSCLC.     

Biological concepts of prolonged neoadjuvant treatment plus GM-CSF in locally advanced tumors

Local treatment with surgery and radiotherapy gives unsatisfactory results in patients with locally advanced cancer. In many cases distant metastases appear shortly after the removal of the primary tumor. Selecting breast cancer as a model for locally advanced disease, we are extrapolating our findings to other solid tumors. Neoadjuvant chemotherapy has improved survival of these patients by downstaging the primary tumors allowing local treatment and early elimination of distant micrometastases. We recently reported in this journal on a study of 42 patients with locally advanced breast cancer (LABC) who received prolonged neoadjuvant chemotherapy of doxorubicin, cyclophosphamide, and GM-CSF prior to surgery and postoperative radiotherapy. These results were promising and prompted us to initiate an international randomized phase III study in which either six neoadjuvant cycles or three neoadjuvant cycles plus three adjuvant cycles are being compared. In LABC patients treated with six neoadjuvant chemoimmunotherapy cycles, we observed a significant rise in the dendritic cell content of the axillary tumor-draining lymph nodes after therapy, associated with an encouraging disease free survival and overall survival. We hypothesize that the prolonged presence of draining lymph nodes in combination with the repeated tumor antigen release, dendritic cell recruitment, and activation may account for the observed increased survival of LABC patients. Based on our findings and the results of preclinical studies, we hypothesize that it is more effective to administer chemotherapy in an extended neoadjuvant regimen, taking advantage of the concurrent biological and immunological processes in the primary tumor and its draining lymph nodes.     

Preoperative induction chemotherapy followed by concurrent chemoradiotherapy in advanced carcinoma of the oral cavity and oropharynx

BACKGROUND: Combined modality therapy plays a central role in the management of advanced head and neck tumors. The objective of our Phase II study was to determine the feasibility, toxicity, and clinical and pathologic response of preoperative induction chemotherapy, followed by concurrent chemoradiotherapy in patients with Stage III or IV squamous cell carcinoma according to the American Joint Committee on Cancer Staging of the oral cavity and oropharynx with no distant metastases. METHODS: After staging, 62 patients with locally advanced carcinoma of the oral cavity and oropharynx were treated preoperatively with chemotherapy (1 cycle of cisplatin and 5-fluorouracil [P-5FU]) followed by concurrent chemoradiotherapy (3 cycles of P-5FU combined with radiotherapy, 60 grays [Gy] given in 33 fractions of 1.8 Gy). After evaluation, patients underwent surgery either as a diagnostic (biopsy) or therapeutic procedure (resection of the primary tumor and/or the neck). Surgery was performed with the intent to spare organ function. RESULTS: Grade 3-4 mucositis was observed in 37 patients (59%). Overall clinical response was obtained in 87%, and the complete clinical response rate was 50%. Surgery was performed in 53 patients, 50 at the primary tumor site (11 biopsies, 14 marginal excisions, and 25 wide excision) and 46 patients had neck dissection. Pathologic complete remission was observed in 29 patients (46%). After a median follow-up of 39 months, locoregional control rate was 76%, estimated 3-year disease free survival rate was 73% (+/- 4%), and estimated 3-year overall survival rate was 76% (+/- 4%). CONCLUSIONS: This intensive multimodality treatment is feasible, and toxicity is significant but tolerable. The treatment results appear promising and durable. Organ-preserving surgery can be performed in many patients.     

Cetuximab in combination therapy: from bench to clinic

Cetuximab, a chimeric IgG₁ monoclonal antibody directed against the ligand-binding domain of the epidermal growth factor receptor, offers a paradigm for the combination of molecularly targeted therapies with cytotoxic agents. In preclinical models, the addition of cetuximab to chemotherapy or radiation therapy enhances antitumor activity. Proposed mechanisms include reducing tumor cell proliferation, angiogenesis, and DNA repair capacity; increasing apoptosis; and inducing cell cycle arrest at treatment-sensitive points. These effects may enhance and restore tumor sensitivity to cytotoxic therapies. In clinical trials, the addition of cetuximab to chemotherapy improves outcomes of patients who had previously failed such agents, as illustrated in irinotecan-resistant and oxaliplatin-refractory metastatic colorectal cancer. As initial therapy, the addition of cetuximab to chemotherapy extends survival in colorectal cancer, lung cancer, and head and neck cancer. Combining cetuximab with radiation therapy extends survival in locally advanced head and neck cancer. As predictive biomarkers are identified, it may become possible to select patients most likely to benefit from such combinations.     

Concomitant therapy with infusion of cisplatin and 5-fluorouracil plus radiation in stage III non-small cell lung cancer

Based on our experience with head and neck cancer, we have developed an every-other-week, split-course schedule for giving combined cisplatin and 5-fluorouracil infusion and radiation to patients with regionally advanced non-small cell lung cancer for a limited number of cycles prior to planned resection. Sixty-four patients having stage III disease without distant metastases were treated with 4 cycles of combined chemotherapy and radiation to 40 Gy and were offered surgical resection. Thirty-nine patients (61%) underwent surgery. Nine had no residual cancer. No correlation was noted between clinical and histologic responses in the surgery group, but histologic response correlated with subsequent outcome. Survival was 58% at 1 year, 33% at 2 years, and 22% at 3 years. Although encouraging, the overall dismal prognosis of this disease has led us to pursue further improvements in protocol design prior to phase III testing of this concept. To this end, etoposide has been added to the above regimen, extending the cycles from every other week to every third week.     

Surgery and chemoradiation in stage IIIA non-small cell lung cancer]

Combination of surgery and radiotherapy has become a standard regimen in multiple cancers. Because of its toxicity and the higher metastatic potential of lung cancer, leading to underestimate the impact of loco-regional treatments, this strategy is currently used only in a clinical trial setting. Recent results from phase III studies comparing surgery and radiotherapy in stage IIIA-N2 locally advanced non-small cell lung cancer after induction treatment showed that surgery should only be performed in patients presenting with a major mediastinal downstaging and possible curative resection within a lobectomy. In all other cases, exclusive chemoradiation remains the therapeutic standard at the time. In this way, all patients with stage III non-small cell lung cancer may receive induction treatment, consisting either in chemotherapy or in sequential or concurrent chemoradiation, which has shown its feasibility and its efficacy regarding tumor response, resectability and local control rates. These two induction regimens are currently compared in randomized trials including stage III resectable and unresectable tumors at time of diagnosis. These developments make treatment of locally advanced non-small cell lung cancer a model for multimodal strategies in oncology, combining chemotherapy, radiotherapy and surgery.     

Docetaxel in the management of patients with head and neck squamous cell carcinoma

The taxanes play a significant role in the treatment of various solid tumors of epithelial origin. Docetaxel is the most extensively studied taxane in prospective head and neck cancer trials and has been investigated as induction chemotherapy or in combination with radiotherapy in locally advanced squamous cell carcinomas of the head and neck (HNSCC) and as palliation in recurrent or metastatic disease. The data in locally advanced disease are particularly compelling. Three recently reported randomized trials, carried out in patients with locally advanced disease who were receiving induction chemotherapy followed by radiotherapy or chemoradiotherapy, demonstrated that adding docetaxel to the standard induction regimen of cisplatin/5-fluorouracil (PF) significantly improved survival compared with PF alone, without significantly increasing toxicity. On the basis of these trials, docetaxel/PF (TPF) has become the current standard induction regimen and TPF-based sequential therapy can be considered a standard treatment alternative to chemoradiotherapy alone in patients with locally advanced HNSCC. This review article discusses the current developments of docetaxel-based chemotherapy and the optimal use of this agent in patients with HNSCC.     

Docetaxel in the management of patients with head and neck squamous cell carcinoma

The taxanes play a significant role in the treatment of various solid tumors of epithelial origin. Docetaxel is the most extensively studied taxane in prospective head and neck cancer trials and has been investigated as induction chemotherapy or in combination with radiotherapy in locally advanced squamous cell carcinomas of the head and neck (HNSCC) and as palliation in recurrent or metastatic disease. The data in locally advanced disease are particularly compelling. Three recently reported randomized trials, carried out in patients with locally advanced disease who were receiving induction chemotherapy followed by radiotherapy or chemoradiotherapy, demonstrated that adding docetaxel to the standard induction regimen of cisplatin/5-fluorouracil (PF) significantly improved survival compared with PF alone, without significantly increasing toxicity. On the basis of these trials, docetaxel/PF (TPF) has become the current standard induction regimen and TPF-based sequential therapy can be considered a standard treatment alternative to chemoradiotherapy alone in patients with locally advanced HNSCC. This review article discusses the current developments of docetaxel-based chemotherapy and the optimal use of this agent in patients with HNSCC.     

Treatment of squamous cell carcinoma of the head and neck with multi-drug chemotherapy and radiotherapy

Multi-drug chemotherapy containing cisplatin has been reported to be one of the most active chemotherapy regimens in advanced or recurrent head and neck squamous cell carcinoma. In this study, the current status of clinical investigation of combination chemotherapies is reviewed. And our data are presented in head and neck cancer with multi-drug chemotherapy containing cisplatin. Thirty-five patients of stage 3-4 and 70 patients with recurrent and/or metastatic head and neck squamous cell carcinoma were treated by multi-drug chemotherapy containing cisplatin, and radiotherapy and/or operation. The overall response rate was 71.4%, with 17.1% complete remission in previously untreated, locally advanced patients and 31.4% in recurrent or metastatic patients. Problems of chemotherapy combined with radiotherapy and future direction of clinical study in locally advanced or recurrent head and neck cancer are discussed.     

Routine brain imaging is unwarranted in asymptomatic patients with rhabdomyosarcoma arising outside of the head and neck region that is metastatic at diagnosis: a report from the Intergroup Rhabdomyosarcoma Study Group.

BACKGROUND: To the authors' knowledge, the incidence of brain metastases at the time of diagnosis in children with metastatic rhabdomyosarcoma (RMS) arising outside the head and neck region is unknown, and routine imaging to identify metastatic brain involvement is costly. METHODS: The authors retrospectively reviewed the results of computed tomography (CT) or magnetic resonance imaging (MRI) scans of the head, which was mandated by protocol, in patients with metastatic RMS arising outside the head and neck region who were enrolled on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV; 1991--1997). RESULTS: Of 100 eligible patients with metastatic RMS arising outside the head and neck region, 56 (56%) underwent head CT (n = 51) and/or MRI (n = 11) scans. Seven of these 56 patients (12.5%) had abnormal scans. Three patients with physical findings suggesting head or neck pathology underwent imaging that confirmed the presence of metastases in bone (one patient), orbit (one patient), or lymph nodes (one patient). One patient who presented with seizures had imaging findings consistent with cerebral embolic infarctions. Of three asymptomatic patients, one had bone metastases that also were identified on skeletal survey and one had bone metastases in the base of the skull that were not identified on bone scan. The remaining asymptomatic patient had a retroperitoneal paraspinal tumor with spinal canal extension and subsequently developed leptomeningeal disease dissemination. CONCLUSIONS: Brain metastases are uncommon at the time of initial diagnosis of metastatic RMS arising outside the head and neck region, and the majority of abnormalities detected on head CT or MRI scans are evident clinically or on other imaging studies. Patients with clinical findings suggesting intracranial pathology and those with paraspinal tumors may benefit from brain imaging, but cost savings may be realized by foregoing imaging in patients without these features.     

Patterns of relapse in locally advanced head and neck cancer patients who achieved complete remission after combined modality therapy

Relapse patterns in patients with locally advanced head and neck cancer who achieved complete remission were evaluated. After combined modality therapy with induction chemotherapy followed by surgery and/or radiotherapy, 71 of 103 patients were clinically free of disease. The 5-year recurrence rate was estimated at 51%, with a 39% local and 26% distant failure rate by 5 years. The factors significantly affecting the relapse patterns were: the site of the primary tumor (those with oral cavity lesions were more likely to fail locally, whereas hypopharynx patients had a higher risk of distant metastases); the type of definitive local treatment (those patients who received surgery and radiotherapy were at lower risk of pure local failure); TN Stage (patients with T4N3 or T3N3 tumor were at higher risk of both local and distant failure); and time to response and presence of oropharyngeal lesions (patients who had a longer period from diagnosis to final complete response [CR] and patients with oropharyngeal primaries were at higher risk for simultaneous local and distant failure). Type of chemotherapy, patient age, tumor differentiation, and response to induction chemotherapy did not significantly influence the patterns of relapse. A combined modality approach with induction chemotherapy, surgery, and/or radiotherapy does not seem to reduce the incidence of distant metastases significantly.