Surgery in the management of small cell lung cancer

OBJECTIVE: We analyzed our experience in the period January 1975-December 1995 aiming to confirm the role of surgery in the multimodality treatment of small cell lung cancer (SCLC). METHODS: 127 patients (5.28% of the overall lung resections for carcinoma) underwent surgery for SCLC. The median age was 60 years (range 34-73). In 87 patients (68.5%) a pre-operative tissue diagnosis was effected and those patients underwent a complete staging procedure. Fifteen patients received up to six complete courses of neoadjuvant and adjuvant chemotherapy. The surgical procedures included: 50 pneumonectomies, 71 lobectomies and six wedge resections. Two patients experienced a local recurrence and a completion pneumonectomy was performed. RESULTS: The median follow-up is 66 months (range 6-214). The 5-year actuarial survival rate is 22.6% (median 18 months). Twenty-three patients are still alive, 21 of them being disease-free. Considering the most conspicuous group of patients (n = 92) treated by surgery and adjuvant chemotherapy, the survival data were 47.2, 14.8 and 14.4% for Stage I, II and III, respectively (P = 0.001). NO patients had a significantly better survival than N1 and N2 patients (P = 0.035). CONCLUSIONS: Surgery and adjuvant chemotherapy might represent an effective form of treatment of limited SCLC without lymph-node involvement. The role of surgery is yet to be verified as regards N1 and N2 status, where even neoadjuvant chemotherapy has not achieved the hoped-for results (no patient reaching a 2-year survival).     

Kaposi''s sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8)--a new human tumour virus

A retrospective analysis of 22 patients with ovarian dysgerminoma who were treated between 1980 and 1987 was carried out. The median age at presentation was 24.5 years. A total of 15 patients were in stage I, one patient was in stage II and six patients were in stage III. Bilateral ovarian involvement was present in four patients. Conservative surgery was carried out in nine patients and 11 patients underwent radical surgery. Two patients had biopsy only. Fourteen patients received adjuvant radiotherapy and three patients received salvage radiation for recurrent disease. The 10-year actuarial survival rate was 81.8%. All 15 patients in stage I were alive and disease-free at a median follow-up of 125 months. Four patients (one in stage II and three in stage III) died of progressive or recurrent abdominopelvic disease. Pelvic recurrence occurred after conservative surgery in two patients in stage IA who had a tumour size greater than 10 cm, but they were salvaged with radical surgery, chemotherapy and radiotherapy. There were seven patients aged 20 years or less. All were alive and disease-free at a median follow-up of 127 months.     

Recurrent pericarditis due to mesalamine hypersensitivity: a pediatric case report and review of the literature

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is an uncommon, aggressive type of endometrial cancer associated with an advanced stage at initial presentation, rapid progression of disease, and poor prognosis. METHODS: Twenty-three patients with UPSC were included in this study. History, treatment, follow-up, and 5-year overall survival probability (5-yr OS%) were evaluated. RESULTS: All women underwent total hysterectomy and bilateral salpingo-oophorectomy. Positive lymph nodes were found in 10 of 17 patients who underwent pelvic lymphadenectomy. Eight patients had FIGO Stage I/II, whereas 15 patients showed Stage III or IV tumors. After surgery 5 women underwent radiotherapy, 5 chemotherapy, and 8 both radiotherapy and chemotherapy. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. Adjuvant irradiation consisted of vault and external beam irradiation. The median duration of follow-up was 39.4 months (25th and 75th percentiles; 26. 1, 68.1). The median overall survival was 43.3 months (12.9, 75th percentile not reached). Three of 10 patients who received only chemotherapy or radiotherapy are alive, whereas 7/8 patients who received a combination of both are alive with no evidence of disease at the time of reporting. The 5-yr OS% was 80% in those who received radio- and chemotherapy and only 30% in those who were treated with radiotherapy alone (log rank = 0.05). CONCLUSION: These results stress the need to study and evaluate the usefulness of combined chemo- and radiation therapy in patients with uterine serous papillary cancer.     

The utility of p53 immunostaining of transbronchial biopsy specimens of lung cancer: p53 overexpression predicts poor prognosis and chemoresistance in advanced non-small cell lung cancer

There are few reports on the p53 status of small cell lung cancer (SCLC) and advanced non-SCLC (NSCLC) because surgically resected specimens are generally not available. Therefore, we evaluated p53 immunostaining in 175 transbronchial biopsy (TBB) specimens obtained from patients with all stages of lung cancer and retrospectively evaluated the relationship between p53 status and clinical parameters. All of the specimens were obtained prior to therapy. Formalin-fixed, paraffin-embedded TBB specimens were immunostained using an anti-p53 antibody (DO-1). p53 protein was detected in 55% (61 of 111) of NSCLCs and 58% (37 of 64) of SCLCs. The rate of positivity increased significantly with increasing stage (stages I and II, 45%; stage III, 54%; stage IV, 66%), but not with other clinical parameters. Ninety-five patients were evaluated for their response to chemotherapy. Positive staining for p53 correlated significantly with unresponsiveness to chemotherapy in NSCLC (response rate of 13 versus 60%; P = 0.006), but not in SCLC (80 versus 57%; P = 0.22). p53 positivity was a statistically significant negative prognostic factor for stage III and stage IV NSCLC (P = 0.02), but not for stage I and stage II NSCLC (P = 0.79). There was no survival difference relative to p53 status in SCLC (P = 0.35). These results indicate that p53 overexpression in TBB specimens predicts poor prognosis and chemoresistance in advanced stage NSCLC.     

Adjuvant radiotherapy and chemotherapy for stage II or IIIA non-small-cell lung cancer after complete resection. Provincial Lung Cancer Disease Site Group

GUIDELINE QUESTIONS: 1) Does the use of postoperative, adjuvant radiotherapy or chemotherapy, alone or in combination, improve survival rates among patients with completely resected, pathologically confirmed stage II or IIIA non-small-cell lung cancer (NSCLC)? 2) Does the use of radiotherapy reduce the risk of local recurrence among patients with completely resected stage II or IIIA NSCLC? OBJECTIVE: To make recommendations about the use of postoperative adjuvant radiotherapy and chemotherapy in the treatment of patients with completely resected stage II or IIIA NSCLC. OUTCOMES: Overall survival and disease-free survival are the primary outcomes of interest. A secondary outcome of interest is local disease control. PERSPECTIVES (VALUES): Evidence was collected and reviewed by 4 members of the Lung Cancer Disease Site Group (Lung Cancer DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The evidence-based recommendation resulting from this review was approved by the Lung Cancer DSG, which comprises medical oncologists, radiation oncologists, pathologists, surgeons and a medical sociologist. A community representative was present at 1 meeting during which the recommendation was discussed. QUALITY OF EVIDENCE: One meta-analysis and 22 randomized controlled trials (RCTs) were published between 1962 and 1996. The RCTs compared surgery plus radiotherapy with surgery alone; surgery plus adjuvant chemotherapy with surgery alone; surgery plus radiotherapy with surgery plus both chemotherapy and radiotherapy. Many studies included patients with stage IIIB NSCLC; some included patients with incompletely resected stage I NSCLC or with small cell lung cancer (maximum 10%). Older studies used chemotherapy or radiation that would now be considered inferior according to current standards of practice. BENEFITS: There was no survival benefit with adjuvant radiotherapy alone, although 3 RCTs reported a reduction in the rate of local recurrence among patients treated with adjuvant radiotherapy. The meta-analysis showed that postoperative, cisplatin-based chemotherapy alone reduced the relative risk of death by 13% (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.74 to 1.02); in combination with radiotherapy it resulted in a 6% reduction in the relative risk of death (HR 0.94, 95% CI 0.79 to 1.11). HARMS: Postoperative adjuvant chemotherapy with alkylating agents was found in the meta-analysis to increase the relative risk of death by 15%. A study involving prolonged adjuvant chemotherapy (busulfan or cytoxan daily for 2 years) reported that 4 of 726 patients had hematologic malignancies. In 1 study, only 53% of patients received all 4 cycles of chemotherapy with cyclophosphamide-doxorubicin-cisplatin (CAP); in another, 22% of patients refused therapy with CAP because of nausea and vomiting. PRACTICE GUIDELINE: There is evidence from RCTs that postoperative radiotherapy reduces rates of local recurrence by 11% to 18% (or 1.6 to 19-fold) among patients with completely resected, pathologically confirmed stage II or IIIA NSCLC. Therefore, if the outcome of interest is a reduction in the frequency of local tumour recurrence, radiotherapy is recommended. However, there is no evidence of a survival benefit from postoperative radiotherapy alone. In a meta-analysis, postoperative chemotherapy with or without radiotherapy resulted in a slightly reduced (statistically nonsignificant) risk of death among patients with surgically resected stage II or IIIA NSCLC. The survival benefit was small and achieved only with chemotherapy regimens that produced substantial toxic effects and that are no longer used. Newer chemotherapy regimens are currently being evaluated as adjuvant therapy, but there is insufficient evidence of benefit at this time to recommend them. Therefore, if the outcome of interest is survival, there is insufficient evidence to recommend current chemotherapy regimens with or without radiotherapy as postoperative, adjuvant the     

Influence of surgery on metachronous distant metastases and survival in rectal cancer

PURPOSE: Total mesorectal excision (TME) and other technical surgical factors reduce local recurrence rate in rectal cancer. Scientific evidence of the positive effect of optimal surgery on survival is locking. Whether a reduction in the incidence of distant metastases can be achieved with optimal surgery is uncertain. We examine the effects of the quality of surgery, as reflected by local recurrence rate, on survival and the incidence of initial distant metastases. PATIENTS AND METHODS: Between 1974 and 1991, 1,581 consecutive patients who underwent curative resection (RO) for rectal carcinoma were monitored for recurrence and survival. TME was introduced in 1985. No patient received adjuvant radiotherapy or chemotherapy. The median follow-up time was greater than 13 years. RESULTS: The local recurrence rate decreased from 39.4% to 9.8% during the study period (P < .0001). The observed 5-year survival rate improved from 50% to 71% (P < .0001). Three hundred six patients with local recurrence had a significantly lower observed 5-year survival rate (P < .0001). A total of 1,285 patients had no local recurrence, but 275 of them developed distant metastases (International Union Against Cancer [UICC] stage I, 8%; stage II, 16%; stage III, 40%). Better-quality surgery had no effect on the incidence of initial distant metastases, which remained constant (P = .44). CONCLUSION: Quality of surgery is an independent prognostic factor for survival in rectal cancer, but has no influence on initial occurrence of distant metastases. Local recurrence cannot be considered an outcome criterion of adjuvant treatment without consideration of the surgeon as a risk factor.     

The lateralizing value of ictal clinical symptoms in uniregional temporal lobe epilepsy

Since 1984, the Cancer and Leukemia Group B (CALGB) has focused its clinical research in stage IV non-small cell lung cancer (NSCLC) on investigations of new agents and combinations. Currently, efforts are aimed at identifying non-cisplatin-based combinations with an increased therapeutic index. In stage III disease multimodality therapies have been pursued. Dillman et al. reported a study comparing standard radiotherapy versus induction chemotherapy followed by radiotherapy in patients with unresectable stage III NSCLC. The chemotherapy-treated patients were found to benefit with a 4-month increase in median survival time compared with patients receiving radiotherapy alone (13.8 vs. 9.7 months) and an increased 3-year survival rate of 23% versus 11%. This was the first randomized cooperative group study demonstrating a survival advantage resulting from the use of induction chemotherapy in locoregionally advanced NSCLC. In a subsequent study, the administration of additional "posterior" chemotherapy was not found to be feasible because of early disease progression and toxicity, while the administration of induction chemotherapy followed by concomitant chemoradiotherapy was feasible; therefore, the latter approach was studied further in a randomized phase III setting. This study compared a standard of two cycles of cisplatin and vinblastine followed by radiotherapy with an experimental arm of cisplatin and vinblastine followed by radiotherapy and concomitant carboplatin. Accrual to this study has been completed and results are expected in the near future. In resectable stage III disease, studies have focused on the optimal sequencing of multimodality therapy. A randomized study comparing standard regional therapy with radiotherapy and surgery versus a previously piloted approach combining chemotherapy, surgery, and radiotherapy was closed prematurely due to poor accrual. The next generation of studies in stage III NSCLC will focus on the integration of new chemotherapy agents into the treatment armamentarium for NSCLC. A randomized phase II study investigating paclitaxel, gemcitabine, and vinorelbine in combination with cisplatin in the induction setting and as concomitant chemoradiotherapy has recently been activated.     

Pure immature teratoma of the ovary: analysis of 22 cases

Between 1970 and 1991, 22 patients with pure immature teratoma were treated at the Center of Oncology in Krakow. Sixteen (72.7%) patients had stage I, four (18.2%) stage II, and two (9.1%) stage III of disease, nine (40.9%) patients had grade 1, 11 (50%) grade 2, and two (9.1%) grade 3 tumors. Eight stage Ia, grade 1 patients were treated with surgery only, the remaining 14 (63.6%) received postoperative chemotherapy. Five-year NED (no evidence of disease) survival was achieved in 81.8% of patients. Out of 16 stage I patients, 15 (93.8%) survived 5-year NED, out of six stage II and III, three (50%) patients only survived this period. We cured all grade 1 patients, and 81.8% (9/11) grade 2; two grade 3 patients died because of tumors. We also cured all six stage Ia patients, treated with unilateral salpingo-oophorectomy (with or without chemotherapy), and all eight stage Ia grade 1 patients treated with surgery only.     

Carboplatin plus epirubicin plus VP-16, concurrent 'split course' radiotherapy and adjuvant surgery for limited small cell lung cancer. Gruppo Oncologico Centro-Sud-Isole (GOCSI)

Thirty-three patients with limited small cell lung cancer (SCLC) received carboplatin, epirubicin and VP-16 chemotherapy, concurrent 'split course' thoracic radiotherapy, followed by surgery for patients achieving an objective response (OR). High-risk patients and those staged T4-N3 (IIIB) at diagnosis, were excluded from surgery. After induction chemoradiotherapy we obtained 90.9% OR, with 63.3% obtaining complete response (CR). Ten patients (30.3%) were eligible for surgery after induction therapy. Five patients (15.1%) were subjected to surgery and five additional patients refused. Of the five patients who were subjected to surgery, four had a complete response (CR), (three pathological confirmations), and one had a partial response (PR), (unresectable). The median survival time for all patients was 16 months with 12.1% of the long-term survivors still living after 2 years and 9% still living after 3 and 4 years. Toxicity consisted mainly of myelosuppression. This study shows a high activity of the chemotherapy and the chemoradiotherapeutic regimen employed but a low feasibility for adjuvant surgery in SCLC.     

Small-cell lung cancer: treatment progress and prospects

Although small-cell lung cancer (SCLC) represents only 20% of all lung cancer cases in the United States, it is the most lethal subtype. Combination chemotherapy unequivocally offers the best chance for improved survival in SCLC. Either PE (platinum plus etoposide) or CAV (cyclophosphamide, Adriamycin, and vincristine) is a reasonable first-line therapy. Alternating PE with CAV does not appear to be significantly superior to PE or CAV alone. Increasing dose intensity, although sometimes associated with higher response rates, does not appear to significantly improve survival and should not be used outside of a clinical study. Several new agents with novel mechanisms of action show promise in treating SCLC. These include: gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), topotecan (Hycamtin), and irinotecan (Camptosar). Given the poor survival and response rates in relapsed patients and the chemoresponsiveness of SCLC, patients with newly diagnosed extensive disease should be encouraged to enroll in phase I or II trials. Thoracic radiotherapy confers a small survival advantage in limited-stage SCLC patients. Although prophylactic cranial irradiation does not significantly improve survival, it does reduce central nervous system (CNS) recurrences with minimal long-term sequelae. Surgery should be considered only for: (1) resection of a solitary pulmonary nodule, which must be followed by adjuvant chemotherapy; and (2) resection of an unresponsive chest tumor, which may harbor a non-small-cell lung cancer component.     

Guideline 'Radiotherapy in non-small-cell lung carcinoma. Working Group, National Organization for Quality Assurance in Hospitals, Netherlands

8000-9000 new patients with lung cancer are diagnosed yearly in the Netherlands. Of these 10-30% can be treated by surgery, which because of co-morbidity or the extent of the disease is impossible in the others. There is agreement on the terms 'curative', 'radical' and 'palliative' radiotherapy: curative radiotherapy aims at cure through destruction of all tumour cells, on the assumption that the neoplasia has not metastasized (this applies to patients with tumours in stage I and II and sometimes in stage III); radical radiotherapy aims at postponement of locoregional tumour growth; this has a positive effect on the patient's duration of survival and quality of life, but it is to be expected that the patient will die from distant metastases (this treatment is indicated for patients with stage IIIA disease); palliative radiotherapy aims at improvement of the quality of life rather than on prolonging the duration of survival. Patients with a stage III tumour (locoregional invasion making surgical treatment impossible but without distant metastases) without complaints should receive radiotherapy, because these patients are candidates for prolonged survival. In the future the best therapy for these patients could be a combined modality (chemotherapy in combination with radiotherapy). Lung cancer patients with an irresectable tumour should be included as often as possible in clinical trials. During treatment checking quality of life, taking into account the objective and the side effects of the treatment, is important. All medical experts who look after the patient, should inform each other on the actual state of health of the patient and any appointments made. A personal file with this information, kept by the patient himself, has been advocated for this purpose.     

Outcome of patients with brain metastases after combined modality therapy in small cell lung cancer (SCLC): a retrospective study

The authors evaluated the role of whole brain radiotherapy (WBRT) on the outcome of brain metastasis and survival in 41 patients with small cell lung cancer (SCLC) treated in their department. In addition to chemotherapy, radiotherapy was given to the primary site in all responder patients. Six patients presented brain metastasis initially and 10 patients after the fourth course of chemotherapy. Brain metastases were symptomatic in 12 of 16 patients with a median time of 5 months (1-14) until symptoms developed. All patients but 2 with brain metastasis received WBRT (30 Gy in 10 fractions) in addition to chemotherapy. The median survival time of patients with brain metastasis was 8.3 months (3.5 to 16) compared to 12 months (4 to 34+) for patients without brain metastasis. In addition, the median survival time for patients with brain metastasis who responded to systemic chemotherapy was better than that of nonresponders. The authors found no improvement in survival in patients who received concomitant WBRT after chemotherapy compared to patients who received WBRT after completion of chemotherapy. In conclusion, the role of consolidating cranial irradiation in addition to chemotherapy in SCLC patients is unclear and warrants prospective randomized studies.     

Whole abdominal external beam radiation in the treatment of primary carcinoma of the fallopian tube

Thirty-two patients with adenocarcinoma of the fallopian tube, treated between 1975 and 1990, were studied. Thirteen patients had stage I disease, 9 stage II, and 10 stage III. All patients underwent bilateral salpingo-oophorectomy, total abdominal hysterectomy, and subcolic omentectomy. All patients received postoperative primary whole abdominal external beam radiotherapy. Seventeen patients (53.1%) of the treated group survived NED for at least 5 years. Survival was 76.9% for stage I, 55.6% for stage II, and 20% for stage III. In the Cox multivariate analysis, two variables were independently related to survival: stage of disease and size of residual disease after surgery. Postoperative teleradiotherapy was totally ineffective in gross residual (>2 cm in diameter) disease (0% 5-year NED survivors) and not effective enough in small residual disease (<2 cm in diameter) (33% 5-year NED survivors). Despite postoperative whole abdominal external beam radiotherapy, 3 patients with microscopic, 4 with small, and 4 with gross residual disease did fail within the peritoneal cavity.     

Thymoma: prognostic factors and treatment outcomes

BACKGROUND: The objective of this study was to establish prognostic factors for thymoma and determine the impact of surgery with or without postoperative radiotherapy. METHODS: Seventy patients treated at the University Hospital Düsseldorf during the period 1954-1991 were retrospectively studied. All thymoma patients underwent surgery, 22 received postoperative radiotherapy, and 3 also received chemotherapy. According to thymoma staging as described previously by Masaoka et al., 21% were Stage I, 26% Stage II, 43% Stage III, 7% Stage IVA, and 3% Stage IVB. Lymphocytic type disease was found in 36% of patients, lymphoepithelial type in 33%, epithelial type in 23%, and spindle cell type in 9%. The relevance of Karnofsky performance status (KPS), gender, age, myasthenia gravis, histology, tumor size, and stage to survival was determined by univariate analysis, and their independent significance was tested by multivariate analysis. Survival rates were calculated using the Kaplan-Meier method and the log rank test. RESULTS: In univariate analysis, KPS (P < 0.001), histologic type (P=0.0093), and stage (P=0.0001) proved to be significant predictors of overall survival. Spindle cell type was associated with the best and epithelial type the worst prognosis; patients with the latter type had a 5-year survival rate of 30%. Multivariate analysis revealed that stage, histology, and KPS were predictive of overall survival. In Stages III and IV, relapses were reduced by postoperative radiotherapy from 50% to 20%. The site of relapse was outside the irradiated area in 80% of patients. Disease free survival (P=0.36) and median survival (P=0.72) of patients with completely resected advanced thymomas did not differ from that for patients with incompletely resected tumors who received radiotherapy. CONCLUSIONS: Postoperative radiotherapy can improve local control in patients with advanced thymoma. Survival after incomplete resection is not compromised when postoperative radiotherapy is employed. KPS should be considered an important prognostic factor in future studies.     

Long-term results following resection for T3 non-small cell lung cancer

Surgical intervention is routinely employed for non-small cell lung cancer, whenever no distant metastasis is found. However, its surgical results depend on the staging of the lung cancer, and surgery for stage III disease is less effective compared with stage I or II disease. For patients with stage III, some treatments such as induction chemotherapy have been tried to support the surgery. Recently, T3 lung cancer is divided in two category of staging, T3N0 is evaluated to be stage II B and T3N1-2 is stage III A. In this study, we classified T3 diseases by some factors, and examined long-term survival of each group. As a result, we concluded that mediastinal invasion and N2 involvement were risk factors to early failure. On the contrary, patients with adjacent lobe invasion and resection of two lobes led to the prolonged survival rather than lobectomy with partial resection of adjacent lobe.     

Randomized trial of epirubicin and cisplatin chemotherapy followed by pelvic radiation in locally advanced cervical cancer. Cervical Cancer Study Group of the Asian Oceanian Clinical Oncology Association

PURPOSE: Pelvic radiation is standard treatment for women with stage IIb to IVa cervical cancer, but treatment results are disappointing, particularly for women with bulky tumors. We investigated the role of primary chemotherapy followed by pelvic radiotherapy in a randomized trial. PATIENTS AND METHODS: Two hundred sixty patients with stage IIb and IVa cervical cancer received either standard pelvic radiotherapy or primary chemotherapy with cisplatin 60 mg/m2 and epirubicin 110 mg/m2 administered at 3-week intervals for three cycles, followed by pelvic radiotherapy. RESULTS: Ninety-nine patients have relapsed with a median follow-up duration of 1.3 years; in 62 patients, the first site of progressive disease was the pelvis. Patients who received primary chemotherapy had a significantly higher pelvic failure rate than those who received radiotherapy alone (P < .003). Seventy-six patients have died, and those who received primary chemotherapy had significantly inferior survival compared with those who received radiotherapy alone (P = .02). Tumor response following chemotherapy was observed in 63%. After radiotherapy, tumor response occurred in 72% of those who received combined modality treatment, compared with 92% of those who received radiotherapy alone. CONCLUSION: Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.     

Serum creatine kinase in fasciocutaneous and musculocutaneous flap surgery

BACKGROUND: Stage III and IV squamous cell cancers of the head and neck are often unresectable at presentation and are associated with poor disease-free and overall survival rates. A phase II study using concurrent cisplatin and radiotherapy in advanced head and neck cancer indicated impressive local-regional control and survival with organ preservation. METHODS: A multicentered phase II study was undertaken consisting of 1.8 Gy fraction radiotherapy for 2 weeks followed by 1.2 Gy BID hyperfractionation to 46.8 Gy. Continuous infusion cisplatin 20 mg/m2 was given on days 1 through 4 and 22 through 25. Biopsy of the primary tumor was done at this point, and patients with clinical and pathologic complete response continued with hyperfractionated radiotherapy to 75.6 Gy plus simultaneous carboplatin 25 mg/m2 BID for 12 consecutive days. Residual disease at 46.8 Gy required curative surgery. RESULTS: Seventy-four patients entered the study, and 73 completed their treatment. Twenty were stage III and 54 were stage IV. Fifty patients had involved regional lymph nodes. Treatment was well tolerated with only one grade IV hematologic toxicity. At 46.8 Gy, biopsy revealed a complete response in 75% of the primary sites and 47% of the nodes. Only 12 patients required resection of the primary lesion. At 4 years (median follow-up is 26 months), 29 patients have recurred. CONCLUSIONS: Accelerated hyperfractionated radiotherapy with concurrent chemotherapy in stage III and IV head and neck cancer yields excellent local-regional control with organ preservation. This protocol is intensive, and some patients have distant failures.     

Treatment of breast cancer with ipsilateral supraclavicular node metastases

During 1954-1977, among 2803 cases of breast cancer 99 (3.5%) had ipsilateral supraclavicular node mestastases. The results of treatment are reported, based on follow-up for more than 10 years. According to the treatment modality, the patients were divided into 4 groups: I. surgery with postoperative adjuvant chemotherapy and radiation therapy; II. radiation and chemotherapy; III. chemotherapy; IV. no treatment. In group I, surgical procedures consisted of segmental mastectomy in 6; simple mastectomy in 7; modified radical mastectomy in 16; standard radical mastectomy in 12, and extended radical mastectomy in 3. The over-all five-year survival rate was 9%. It was 18% (8/44) in group I, but only 5% (1/21) in group II. None survived for 5 years in group III and group IV. The results seem to indicate that more aggressive multi-modality treatment of breast cancer with ipsilateral supraclavicular lymph node metastases is indicated to expect better survival.     

Second lung cancers in patients successfully treated for lung cancer

The rate of developing second lung cancers and other aerodigestive tumors in patients who have been treated for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is approximately 10-fold higher than other adult smokers. The risk of second lung cancers in patients surviving resection of NSCLC is approximately 1% to 2% per year. The series reported show that the patients who develop second NSCLCs tend to have early-stage NSCLC (predominantly stage I and II). The survival of patients after the second resection of lung cancer is similar to that of patients presenting with initial NSCLC. The risk of second lung cancers in patients surviving SCLC is 2% to 14% per patient per year and increases two- to seven-fold with the passage of time from 2 to 10 years. The risk of second lung cancers in patients treated for SCLC appears to be higher than that found in patients with NSCLC who were treated only with surgical resection. In addition, the chances of successful resection of second primary NSCLCs in patients who were treated for SCLC is much less than that for patients with metachronous lung cancers after an initial NSCLC. Patients treated for SCLC who continue to smoke cigarettes increase their rate of developing second lung cancers. The contribution of chest radiation and chemotherapy administration to the risk of developing second lung tumors remain to be defined but may be responsible for some of the increased risk in patients treated for SCLC compared to patients undergoing a surgical resection for NSCLC.     

Treatment-related leukemia in breast cancer patients treated with fluorouracil-doxorubicin-cyclophosphamide combination adjuvant chemotherapy: the University of Texas M.D. Anderson Cancer Center experience

PURPOSE: Adjuvant chemotherapy for breast cancer has been the routine practice in the past decade. A number of studies have observed an increased incidence of treatment-related leukemias following chemotherapy with alkylating agents and/or topoisomerase II inhibitors. We evaluated the incidence of treatment-related leukemias in breast cancer patients treated in four adjuvant and two neoadjuvant chemotherapy trials at The University of Texas M.D. Anderson Cancer Center. PATIENTS AND METHODS: Between 1974 and 1989, 1,474 patients with stage II or III breast cancer were treated in six prospective trials of adjuvant (n = 4) or neoadjuvant (n = 2) chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (CTX) (FAC) with or without other drugs. The median observation time was 97 months. In 1,107 patients, FAC chemotherapy was given postoperatively; 367 patients received induction chemotherapy, as well as postoperative chemotherapy. Eight hundred ten patients had surgery followed by radiotherapy and chemotherapy; 664 patients had surgery and chemotherapy only. Patients in two adjuvant and one neoadjuvant study received higher cumulative doses of CTX compared with those in the other studies. RESULTS: Fourteen cases of leukemia were observed. Twelve of these patients had received radiotherapy and chemotherapy, and two had received chemotherapy only. Six of the reported patients with leukemia were treated with a cumulative CTX dose of greater than 6 g/ m2. Five of these patients had received both radiotherapy and chemotherapy. The median latency period in the 14 patients was 66 months (range, 22 to 113). Six of 10 patients with adequate cytogenetic analyses had abnormalities that involved chromosomes 5 and/or 7. The rest of the patients had nonspecific cytogenetic abnormalities or lacked cytogenetic information. The 10-year estimated leukemia rate was 1.5% (95% confidence interval [CI], 0.7% to 2.9%) for all patients treated, 2.5% (95% CI, 1.0% to 5.1%) for the radiotherapy-plus-chemotherapy group, and 0.5% (95% CI, 0.1% to 2.4%) for the chemotherapy-only group; this difference was statistically significant (P = .01). The 10-year estimated leukemia risk for the higher-dose (> 6 g/m2) CTX group was 2% (95% CI, 0.5% to 5.0%) compared with 1.3% (95% CI, 0.4% to 3.0%) for the lower-dose group, a difference that was not statistically significant (P = .53). CONCLUSION: These data illustrate that patients treated with adjuvant FAC chemotherapy plus radiotherapy have a slightly increased risk of leukemia. This information needs to be considered in the treatment plans for patients with breast cancer. However, for most patients, the benefits of adjuvant therapy exceed the risk of treatment-related leukemia.