18fluorodeoxyglucose positron emission tomography to detect mediastinal or internal mammary metastases in breast cancer.

PURPOSE: To determine the prevalence of suspected disease in the mediastinum and internal mammary (IM) node chain by 18fluorodeoxyglucose (FDG) positron emission tomography (PET), compared with conventional staging by computed tomography (CT) in patients with recurrent or metastatic breast cancer. PATIENTS AND METHODS: We retrospectively evaluated intrathoracic lymph nodes using FDG PET and CT data in 73 consecutive patients with recurrent or metastatic breast cancer who had both CT and FDG PET within 30 days of each other. In reviews of CT scans, mediastinal nodes measuring 1 cm or greater in the short axis were considered positive. PET was considered positive when there were one or more mediastinal foci of FDG uptake greater than the mediastinal blood pool. RESULTS: Overall, 40% of patients had abnormal mediastinal or IM FDG uptake consistent with metastases, compared with 23% of patients who had suspiciously enlarged mediastinal or IM nodes by CT. Both FDG PET and CT were positive in 22%. In the subset of 33 patients with assessable follow-up by CT or biopsy, the sensitivity, specificity, and accuracy for nodal disease was 85%, 90%, and 88%, respectively, by FDG PET; 54%, 85%, and 73%, respectively, by prospective interpretation of CT; and 50%, 83%, and 70%, respectively, by blinded observer interpretation of CT. Among patients suspected of having only locoregional disease recurrence (n = 33), 10 had unsuspected mediastinal or IM disease by FDG PET. CONCLUSION: FDG PET may uncover disease in these nodal regions not recognized by conventional staging methods. Future prospective studies using histopathology for confirmation are needed to validate the preliminary findings of this retrospective study.

High-dose melphalan, etoposide, total-body irradiation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing's sarcoma does not improve prognosis.

PURPOSE: To determine whether consolidation therapy with high-dose melphalan, etoposide, and total-body irradiation (TBI) with autologous stem-cell support would improve the prognosis for patients with newly diagnosed metastatic Ewing's sarcoma (ES). PATIENTS AND METHODS: Thirty-two eligible patients with newly diagnosed ES metastatic to bone and/or bone marrow were enrolled onto this study. Treatment was initially comprised of five cycles of induction chemotherapy (cyclophosphamide, doxorubicin, and vincristine alternating with ifosfamide and etoposide) and local control. Peripheral-blood stem-cell collection was performed after the second cycle of chemotherapy, with delay if the bone marrow was persistently involved. If patients had a good response to initial therapy, they proceeded to consolidation therapy with melphalan, etoposide, TBI, and stem-cell support. RESULTS: Of the 32 eligible patients, 23 proceeded to high-dose therapy consolidation. Of the nine patients who did not proceed to consolidation, four were secondary to progressive disease and two were secondary to toxicity. Three patients died from toxicity during the high-dose phase of the therapy. The majority of the patients who underwent high-dose consolidation therapy experienced relapse and died with progressive disease. Two-year event-free survival (EFS) for all eligible patients is 20%. The 2-year post-stem-cell reconstitution EFS for the subset of 23 patients who received consolidation therapy is 24%. Analysis of peripheral-blood stem-cell collections by molecular techniques for minimal residual disease showed contamination of at least some samples by tumor cells in all three patients with available data. CONCLUSION: Consolidation with high-dose melphalan, etoposide, TBI, and autologous stem-cell support failed to improve the probability of EFS in this cohort of patients with newly diagnosed metastatic ES.

Concurrent radiation therapy and paclitaxel or docetaxel chemotherapy in high-risk breast cancer.

PURPOSE: Evidence supports the inclusion of the taxanes in the treatment of breast cancer. A recent randomized trial has shown a survival advantage to the addition of paclitaxel in the adjuvant treatment of node-positive patients. Several studies have suggested diminished local control if adjuvant radiation is delayed, while in vitro and in vivo studies have demonstrated a benefit of concurrent administration of taxanes with radiation. For these reasons, we began in 1995 to administer radiation therapy concurrently with the taxanes in advanced breast cancer. This retrospective review examines the feasibility of such treatment. METHODS AND MATERIALS: Forty-four patients were treated with concurrent radiation and either paclitaxel (29 patients) or docetaxel (15 patients). One patient received both paclitaxel and docetaxel. Eighteen patients were treated for recurrent disease, 9 had received prior radiation. Toxicity was assessed by the RTOG scale for acute and late effects. RESULTS: Concurrent radiation and taxane chemotherapy was well tolerated. Nine patients (20%) experienced Grade 3 acute skin toxicity. This was more likely with docetaxel than paclitaxel (p = 0. 04). Among patients undergoing breast conservation, there were no Grade 3 toxicities. With a median follow-up of 11 months, 1 patient has developed breast fibrosis. CONCLUSION: Concurrent administration of both paclitaxel and docetaxel with radiation resulted in acceptable toxicity. Overall, the acute skin toxicity seen with docetaxel was more pronounced. However, among patients undergoing breast conservation the taxanes were both well tolerated. Further study is necessary to assess the impact of concurrent treatment on long-term outcome.

Digital radiotherapy simulator.

We describe a prototype digital radiotherapy simulator which consists of a conventional simulator gantry, digital spot imager, and image correction and reconstruction software. The ability of the digital spot imager to acquire a diagnostic quality image directly in digital format during simulation offers unique possibilities in clinical practice. Applications include prescription of multileaf collimator, on-line patient setup verification, remote consultation and treatment planning. In addition, we discuss the possibility of using the digital simulator as a volume-CT scanner capable of obtaining three-dimensional anatomical information in a single scan.

Fast neutrons in prostatic adenocarcinomas: worldwide clinical experience.

Primary tumor control remains a major problem in the treatment of locally advanced prostate carcinoma. Clinical local failure rates approach 30-40% and may be significantly higher when results of prostatic biopsy or prostate-specific antigen (PSA) levels are considered. The low growth rate and cycling fraction of prostate adenocarcinoma suggest potential therapeutic advantage for the high linear energy transfer (LET) of neutrons. The Radiation Therapy Oncology Group (RTOG) performed a multi-institutional randomized trial (RTOG 77-04) comparing mixed beam (neutron plus photon) irradiation to conventional photon irradiation for the treatment of locally advanced prostate cancer. A subsequent trial by the Neutron Therapy Collaborative Working Group (NTCWG 85-23) compared pure neutron irradiation to standard photon irradiation. Both randomized trials demonstrate significant improvement in locoregional control with neutron irradiation compared to conventional photon irradiation in the treatment of locally advanced prostate carcinoma. To date, only the mixed beam trial has shown a significant survival benefit. Future analysis of the larger NTCWG trial at the 10-year point should confirm whether or not improved locoregional control translates into a survival advantage. These findings have significant implications for all local treatment strategies including dose-escalated conformal photon irradiation, prostate implantation, and neutron radiation. Given the large numbers of patients afflicted with this disease, a positive survival advantage for neutrons or mixed beam therapy would provide a strong incentive for the development of economically feasible clinical neutron facilities.

High-dose induction chemoradiotherapy followed by autologous bone marrow transplantation as consolidation therapy in rhabdomyosarcoma, extraosseous Ewing's sarcoma, and undifferentiated sarcoma.

PURPOSE: To improve response and survival rates in patients with high-risk rhabdomyosarcoma (RMS), extraosseous Ewing's sarcoma, and undifferentiated sarcoma, we used a short course of induction with multi-agent chemotherapy, hyperfractionated radiotherapy, and surgery when possible. Consolidation was with intensive chemotherapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Twenty-six patients (21 with RMS, three with undifferentiated sarcoma, and two with extraosseous Ewing's sarcoma) were entered onto the protocol between June 1990 and March 1994. Induction consisted of ifosfamide, etoposide, doxorubicin, dactinomycin, cyclophosphomide, and vincristine, and a split course of hyperfractionated radiotherapy. Patients who attained a complete response (CR) or good partial response (GPR) received consolidation with high-dose melphalan and etoposide followed by ABMT. RESULTS: Of 26 previously untreated patients 19 (73%) achieved a CR (n=13) or GPR (n=6) at the completion of induction and underwent ABMT. Two-year overall survival (OS) was 56% (95% confidence interval [CI], 36% to 76%) and progression-free survival (PFS) was 53% for the whole group (95% CI, 33% to 73%). CONCLUSION: Consolidation of response by myeloablative chemotherapy was well tolerated. Split-course hyperfractionated radiotherapy did not increase the rate of local control. The results of this short-course therapy were comparable to previous therapies of 1 to 2 years' duration. Induction and consolidation chemotherapy, as well as radiation dose, could be further intensified, since no death due to toxicity occurred among these patients.

Asymptomatic recurrence detection with surveillance scanning in children with medulloblastoma.

PURPOSE: To assess the utility of surveillance neuroimaging in detecting recurrent disease in patients treated for medulloblastoma. PATIENTS AND METHODS: Records and scans of 59 consecutive patients treated for medulloblastoma between 1984 and 1993 in one institution were retrospectively reviewed. RESULTS: Nineteen of 59 patients had recurrence of tumor, of which 17 were available for this study. Eleven of the 17 recurrent patients were asymptomatic at the time of detection. The median time to recurrence was 13 months (range, 3 to 90). CONCLUSION: Surveillance scanning detected a majority of recurrences before onset of symptoms. Although the outcome of those with recurrent disease remains poor, early detection with minimum disease provides the best setting in which to test newer therapies. Patients and their parents also were more likely to elect pursuing further treatment when relapse was detected asymptomatically.

The potential role of external beam radiation in preventing restenosis after coronary angioplasty.

The potential role of radiation in the prevention of coronary artery restenosis after angioplasty has generated much recent interest. Animal research and pilot clinical efforts have focused primarily on intraluminal methods of radiation delivery. This article reviews the experience to date with external beam radiation in restenosis prevention and suggests issues that should be considered from the standpoint of both external beam and intravascular radiotherapy. External beam radiation can certainly play an effective role in clinical studies of coronary artery restenosis, and a multicenter randomized trial of external beam radiation after coronary angioplasty has been initiated.

Medulloblastoma: long-term results for patients treated with definitive radiation therapy during the computed tomography era.

PURPOSE: We performed a retrospective evaluation of the patterns of failure and outcome for medulloblastoma patients treated with craniospinal irradiation therapy during the computed tomography (CT) era. MATERIALS AND METHODS: The records of 100 patients treated at Memorial Sloan-Kettering Cancer Center between 1979 and 1994 were reviewed. CT scans or magnetic resonance imaging were used to guide surgical intervention and evaluate the extent of resection postoperatively. All patients were treated with conventional fractionation (1.8 Gy/day) and the majority received full-dose neuraxis radiation therapy and > 50 Gy to the primary site. RESULTS: With a median follow-up of 100 months, the median, 5-year, and 10-year actuarial overall survival for the entire group were 58 months, 50%, and 25%, respectively. The median, 5- and 10-year actuarial disease-free survivals were 37 months, 41%, and 27%, respectively. Patients with localized disease (no evidence of disease beyond the primary site) had significantly improved overall (p < 0.02) and disease-free (p < 0.02) survivals compared to those with nonlocalized disease. For patients with localized disease, the 5- and 10-year overall survival rates were 59% and 31%, whereas the disease-free survivals were 49% and 31%, respectively. Disease-free and overall survivals at similar intervals for patients with nonlocalized disease were 29% and 30% (5 years), and 29% and 20% (10 years), respectively. Sixty-four of 100 patients failed treatment. Local failure as any component of first failure occurred in 35% of patients or 55% (35 of 64) of all failures and as the only site of first failure in 14% or 22% (14 of 64) of all failures. For patients presenting with localized disease (n = 68), local failure as any component of first failure occurred in 32% (22 of 68) and in 18% (12 of 68) as the only site. A multivariate analysis showed that M stage was the only prognostic factor to influence overall survival. For disease-free survival, M stage and the extent of resection were prognostic factors. Ventriculoperitoneal shunting and the use of chemotherapy were associated with a poor outcome; however, these results were confounded by the positive impact of chemotherapy in decreasing the risk of extraneural metastases and the use of these therapies in the more advanced patients. CONCLUSION: These long-term follow-up data represent one of the largest series of patients with complete follow-up who were treated with a consistent radiation therapy treatment policy during the CT era. Local failure in patients with localized disease, the persistent risk of late failures, treatment-related toxicity, and the ever-present risk of secondary malignancies demonstrate the limitations of standard therapies. Strategies used to increase the total dose to the primary site should be pursued along with other adjuvant therapies such as intensive chemotherapy.

Neutron radiotherapy for adenoid cystic carcinoma of minor salivary glands.

PURPOSE: To examine the efficacy of fast neutron radiotherapy for the treatment of patients with locally advanced, adenoid cystic carcinoma of minor salivary glands and to identify prognostic variables associated with local control, overall survival, and cause specific survival. METHODS AND MATERIALS: Eighty-four patients having adenoid cystic carcinoma of minor salivary glands were treated with fast neutron radiotherapy during the years 1985-1994. All patients had either unresectable disease or gross disease remaining after attempted surgical extirpation. Seventeen patients had previously received conventional radiotherapy and their subsequent treatment fields and doses for neutron radiotherapy were modified for critical sites (brainstem, spinal cord, brain). Although the median doses (tumor maximum and tumor minimum) only varied by < or = 10%, treatment portals were substantially smaller in these patients because of normal tissue complication considerations. Twelve patients (13%) had distant metastases at the time of treatment and were only treated palliatively with smaller treatment portals and lower median tumor doses (< or = 80% of the doses delivered to curatively treated patients). Seventy-two patients were treated with curative intent, with nine of these having recurrent tumors after prior full-dose radiotherapy. The median duration of follow-up at the time of analysis was 31.5 months (range 3-115). Sites of disease and number of patients treated per disease site were as follows: paranasal sinus-31; oral cavity-20; oropharynx-12; nasopharynx-11; trachea-6; and other sites in the head and neck-4. RESULTS: The 5-year actuarial local-regional tumor control rate for all patients treated with curative intent was 47%. Patients without involvement of the cavernous sinus, base of skull, or nasopharynx (51 patients) had a 5-year actuarial local-regional control rate of 59%, whereas local-regional control was significantly lower (15%) for patients with tumors involving these sites (p < 0.005). In the latter cases, normal tissue injury considerations precluded delivery of the full dose to the entire tumor. Patients with no history of prior radiotherapy (63 patients) had an actuarial local control rate of 57% at 5 years compared to 18% for those (9 patients) who had been previously irradiated with conventional photons (p = 0.018). Eliminating the dose-limiting factors of prior radiation therapy and/or high risk sites of involvement, the 5-year actuarial local-regional control rate for these 46 patients was 63%, with an actuarial cause specific survival rate of 79%. Lymph node status was a predictor of distant metastasis: 57% of node positive patients developed distant metastases by 5 years compared to 15% of patients with negative nodes (p < 0.0005), and patients who had nodal involvement developed distant metastases sooner than node negative patients (p < 0.0001). The 5-year actuarial overall survival and cause specific survival for the 72 patients treated with curative intent were 59% and 64%, respectively. CONCLUSIONS: Fast neutron radiotherapy offers high local-regional control and survival rates for patients with locally advanced, unresectable adenoid cystic carcinomas of minor salivary glands. It should be considered as initial primary treatment for these patients, as well as for other patients in whom surgical extirpation would cause considerable morbidity.

Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy.

PURPOSE: To test intensive alkylator-based therapy in desmoplastic small round-cell tumor (DSRCT). PATIENTS AND METHODS: Patients received the P6 protocol, which has seven courses of chemotherapy. Courses 1, 2, 3, and 6 included cyclophosphamide 4,200 mg/m2, doxorubicin 75 mg/m2, and vincristine (HD-CAV). Courses 4, 5, and 7 consisted of ifosfamide 9 g/m2 and etoposide 500 mg/m2 for previously untreated patients, or ifosfamide 12 g/m2 and etoposide 1,000 mg/m2 for previously treated patients. Courses started after neutrophil counts reached 500/microL and platelet counts reached 100,000/microL. Tumor resection was attempted. Post-P6 treatment options included radiotherapy and a myeloablative regimen of thiotepa (900 mg/m2) plus carboplatin (1,500 mg/m2), with stem-cell rescue. RESULTS: Ten previously untreated and two previously treated patients have completed therapy. The male-to-female ratio was 11:1. Ages were 7 to 22 years (median, 14). The largest masses were infradiaphragmatic (n = 11) or intrathoracic (n = 1). Other findings included serosal implants (n = 11), regional lymph node invasion (n = 8), ascites or pleural effusion (n = 7), and metastases to liver (n = 5), lungs (n = 4), distant lymph nodes (n = 3), spleen (n = 2), and skeleton (n = 2). Tumors uniformly responded to HD-CAV, but there were no complete pathologic responses. One patient died at 1 month from tumor-related Budd-Chiari syndrome. Of seven patients who achieved a complete remission (CR), five remain in CR 9, 12, 13, 33, and 38 months from the start of P6, one patient died of infection at 12 months (autopsy-confirmed CR), and one patient relapsed 4 months off therapy. Of four patients who achieved a partial remission (PR), one remains progression-free at 34 months and three developed progressive disease. Five patients received local radiotherapy: three were not assessable for response, but in two patients, antitumor effect was evident. Four patients received thiotepa/carboplatin: two were in CR and remain so, and two patients had measurable disease that did not respond. CONCLUSION: For control of DSRCT, our experience supports intensive use of HD-CAV, aggressive surgery to resect visible disease, radiotherapy to high-risk sites, and myeloablative chemotherapy with stem-cell rescue in selected cases.

High-dose chemotherapy with autologous marrow rescue for malignant brain tumors: analysis of the impact of prior chemotherapy and cranio-spinal irradiation on hematopoietic recovery.

The relative impact of age, sex, nucleated cell dose, prior chemotherapy, prior cranio-spinal irradiation (CSI) and bone marrow harvest (BMH) site on hematological recovery after ABMT were analyzed in a multivariate model. The study population comprised 100 patients with a median age of 9 years who underwent ABMT for malignant brain tumors. Two engraftment parameters were evaluated: number of days post ABMT before (1) an absolute neutrophil count (ANC) > or = 0.5 x 10(9)/l and (2) a platelet count > or = 50 x 10(9)/I were achieved for the third consecutive day without transfusions. Increasing cell dose correlated significantly with a more prompt recovery of platelet counts and ANC. Previous chemotherapy significantly delayed both neutrophil and platelet engraftment. The group of patients who also received CSI had a very delayed platelet recovery with a median time to engraftment of 72 days. Neutrophil engraftment was also significantly delayed and occurred at a median of 23 days. This effect of CSI was independent of cell dose or prior chemotherapy. In 20 of these patients, marrow was harvested at least partially from the posterior iliac crests, which might have received significant doses of irradiation. We conclude that engraftment is significantly faster if bone marrow is harvested prior to any chemotherapy administration, and that patients who receive prior CSI may have significant engraftment delay, particularly of the platelet lineage. In this latter group of patients, marrow should not be harvested from the posterior iliac crests. Strategies that might enhance both neutrophil and platelet count recovery should be considered in patients with irradiation damage to a substantial proportion of the total hematopoietic tissue.

Clinical trials of neutron radiotherapy in the United States.

The development of clinical neutron facilities in the 1980s, capable of delivering high energy neutrons spurred full scale phase III testing of neutron beam radiotherapy in a number of tumors including salivary gland, head and neck, prostate, and non small-cell lung cancer. The Radiation Therapy Oncology Group (RTOG) and the Medical Research Council (MRC) jointly sponsored a randomized trial for the treatment of advanced stage salivary gland tumors comparing neutron to conventional photon and/or electron radiotherapy. Although no improvement in survival was seen, the study demonstrated a striking and statistically significant difference in the local-regional control of unresectable salivary gland tumors (56 vs 17%), favoring neutron beam irradiation. Subsequent clinical trials of neutron beam irradiation were initiated by the Neutron Therapy Collaborative Working Group (NTCWG) sponsored by the National Cancer Institute (NCI). A phase III trial comparing neutron to photon radiotherapy for inoperable regional non-small cell lung cancer showed no overall improvement in survival. However, a statistically significant improvement in survival was observed in the subset of patients with squamous cell histology. The NTCWG trial comparing fast-neutron therapy versus conventional photon irradiation in the treatment of advanced squamous cell carcinomas of the head and neck showed a statistically significant improvement in initial complete response (70 vs 52%) favoring neutrons. However, subsequent failures erased any difference in ultimate local-regional control rates and survival curves were essentially the same in both arms. The randomized study of the NTCWG for locally advanced prostate cancer demonstrated a significant decrease in local-regional failure (11 vs 32%) at 5 years, favoring the neutron arm. Furthermore, biochemical measures of disease control also favored the neutron arm with prostate specific antigen (PSA) levels elevated in 17% of the neutron-treated patients compared to 45% of the photon-treated patients at 5 years. At the 5-year analysis, no significant difference in survival was observed between the two arms; however, longer follow-up is necessary to assess the ultimate impact of improved local-regional control on survival. An analysis of complications in this series revealed the importance of beam shaping and treatment planning capabilities in maintaining long-term sequelae following neutron irradiation at an acceptably low level.

Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography.

PURPOSE: Recent clinical investigations have shown a strong correlation between pretreatment tumor hypoxia and poor response to radiotherapy. These observations raise questions about standard assumptions of tumor reoxygenation during radiotherapy, which has been poorly studied in human cancers. Positron emission tomography (PET) imaging of [F-18]fluoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated radiotherapy to systematically evaluate changes in tumor oxygenation. METHODS AND MATERIALS: Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while receiving primary radiotherapy. Computed tomograms were used to calculate tumor volumes, define tumor extent for PET image analysis, and assist in PET image registration between serial studies. Fractional hypoxic volume (FHV) was calculated for each study as the percentage of pixels within the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio > or = 1.4 by 120 min after injection. Serial FHVs were compared for each patient. RESULTS: Pretreatment FHVs ranged from 20-84% (median 58%). Subsequent FHVs varied from 8-79% (median 29%) at midtreatment, and ranged from 3-65% (median 22%) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size and pretreatment FHV. CONCLUSIONS: Although there is a general tendency toward improved oxygenation in human tumors during fractionated radiotherapy, these changes are unpredictable and may be insufficient in extent and timing to overcome the negative effects of existing pretreatment hypoxia. Selection of patients for clinical trials addressing radioresistant hypoxic cancers can be appropriately achieved through single pretreatment evaluations of tumor hypoxia.

Stage 4 neuroblastoma diagnosed at more than 1 year of age: gross total resection and clinical outcome.

The importance of gross total resection of the primary tumor in stage 4 neuroblastoma is controversial. The purpose of this study was to assess the impact of gross total resection of the primary tumor on clinical outcome in patients with stage 4 neuroblastoma diagnosed at more than 1 year of age. The authors retrospectively analyzed 70 newly diagnosed cases treated with one of five regimens of increasing dose-intensity. Outcome variables included survival time from diagnosis, and time to local recurrence or local tumor progression. Patient variables analyzed for impact on survival included age, anatomic location of the primary tumor, radiation treatment of the primary site, complete resection at diagnosis, gross total resection (GTR) at any time in the course of therapy, and treatment protocol dose-intensity. GTR was accomplished in seven patients at the time of diagnosis and in 32 patients after chemotherapy. The likelihood of complete gross resection after chemotherapy increased with greater protocol intensity. The only patient variables that correlated with improved survival were GTR (P = .03) and chemotherapy protocol (P = .01). GTR was also associated with improved local control. Although an independent effect of GTR on survival was not demonstrable because complete resection after chemotherapy correlated strongly with increasing protocol intensity, its association with improved overall survival was striking. These results support a continued role for GTR in high-risk neuroblastoma, along with intensive chemotherapy.

Visual outcomes of macular retinoblastoma after external beam radiation therapy.

PURPOSE: To determine the risk factors that influence the visual outcomes of patients with macular retinoblastoma who are treated with radiation therapy. METHODS: The medical records of all patients with macular retinoblastoma treated with radiation therapy between 1980 and 1990 were reviewed. Ten patients were entered into the study. Features analyzed included patient age, laterality of eye involvement, location and size of macular tumor(s) at the time of diagnosis, treatment course, and most recent visual acuity. FINDINGS: Ten of 11 eyes (10 patients) were successfully treated with external beam radiation. Eight patients obtained visual acuities ranging from 20/25 to 20/100; two patients had visual acuities of 20/200 or less. The best visual acuities were noted in patients whose tumor(s) did not involve the fovea and were relatively small. The worse visual acuities were noted in patients with binocular vision whose tumors invaded the fovea and were larger in size. In two of three patients in whom both eyes were retained, superimposed amblyopia developed in the eye with macular retinoblastoma. CONCLUSION: The authors' findings indicate that most patients with macular retinoblastoma who are treated with external beam radiation have favorable visual outcomes, but final visual acuity depends on the size of the tumor and involvement of the fovea. Patients in whom both eyes are retained are predisposed to further visual loss from amblyopia.

Primary peripheral nodal lymphoma in children.

BACKGROUND: In this series of 208 pediatric patients with non-Hodgkin (NHL) studied from 1971 to 1986, 84 patients (40.4%) had nodal lymphomas; 40 (19.2%) of these patients had peripheral nodal lymphoma and 44 (21.2%) had mediastinal lymphoma. METHODS: Forty pediatric patients with primary peripheral nodal lymphoma were treated at Memorial Sloan-Kettering Cancer Center with the LSA2-L2 protocol from July 1971 to January 1986. Informed consent was obtained from all patients and/or guardians. RESULTS: There were 26 male patients and 14 female patients, with a median age of 10 years. Two patients had Stage I disease, 5 Stage II, 9 Stage III, 8 Stage IVA (< 25% blasts in the bone marrow), and 16 Stage IVB (> 25% blasts in the bone marrow). The last patient with Stage IVB disease was entered in 1977, a time when the philosophy of treatment for leukemia-lymphomas had not yet evolved completely. Most of these lymphomas were high-grade lymphoblastic lymphomas, followed by immunoblastic lymphomas and reticulosarcomas. The event-free survival rate of this group of patients was 75%, with all patients having completed therapy, and a median observation time of more than 10 years without therapy. The lymphoma-free survival rate was 80%. Sex, age, and stage were not of prognostic significance. There was no significant difference in survival between patients with lymphoblastic and histiocytic lymphomas (75% versus 64%, respectively). There was no significant difference in survival between the patients with high-grade and medium-grade lymphomas (75% versus 78%, respectively). Lactic dehydrogenase (LDH) in this primary site was not indicative of extent or bulk of disease and did not affect survival negatively. Radiation therapy and dose intensity of chemotherapy influenced survival by promoting rapid and more complete cell kill, helping prevent the emergence of resistant cells. CONCLUSIONS: Although primary peripheral nodal lymphoma usually is disseminated at diagnosis, it is still a highly curable disease when treated aggressively. The lymphoma-free survival rate for patients with primary nodal NHL with marrow involvement is 75%, and this subsequently has led to a different philosophy in the treatment of high-risk leukemias and lymphoma-leukemias with the NY-I and NY-II protocols, with excellent results.

Treatment-related esophageal stricture in pediatric patients with cancer.

BACKGROUND: Intensive antineoplastic regimens have enhanced long-term survival in pediatric patients with cancer, but can result in long-term complications. Esophageal stricture formation is one such complication. METHODS: We reviewed the experience with benign esophageal stricture in pediatric patients with cancer over the past 15 years in a major cancer center. Clinical course, along with endoscopic, radiologic, and manometric esophageal studies, was reviewed. RESULTS: Esophageal strictures formed in five pediatric patients who were treated with radiation and/or chemotherapy. Stricture formation was associated with abnormal esophageal motility in four out of the five patients. Repeated esophageal dilation was performed from 3-50 times and resulted in stricture resolution in only 2 of the 5 patients. CONCLUSIONS: Esophageal stricture formation in this population is rare, but is associated with long-term morbidity.