The effect of systemic therapy on local-regional control in locally advanced breast cancer.

One hundred and seven patients with locally advanced breast cancer were prospectively referred for multimodality treatment on protocol using chemohormonal therapy to maximal response followed by local treatment and maintenance therapy. Forty-eight patients (45%) were diagnosed with Stage IIIA disease, 46 (43%) with Stage IIIB inflammatory cancer, and 13 (12%) with Stage IIIB non-inflammatory disease. Induction therapy consisted of cyclophosphamide, doxorubicin, methotrexate, and 5-fluorouracil with hormonal synchronization using tamoxifen and conjugated estrogens. Local treatment was determined by response to chemotherapy. Patients with a clinical parital response underwent mastectomy followed by local-regional radiotherapy while patients with a clinical complete response were biopsied for pathologic correlation. Those with residual disease received mastectomy followed by radiotherapy while those with a pathologic complete response received radiation only to the intact breast and regional nodes. With a median follow-up of 64 months, patients with IIIA disease had a significantly lower local-regional failure rate compared to IIIB inflammatory patients, with the 5-year actuarial local-regional failure rate as only site of first failure 3% for IIIA disease versus 21% for IIIB inflammatory cancer (p = .02), and local-regional failure as any component of first failure 12% versus 36% (p = .01), respectively. When local-regional failure was analyzed by repeat biopsy, 5/31 (16%) patients with a pathologic complete response treated with radiation only developed a local-regional failure versus 2/53 (4%) with residual disease treated with mastectomy and postoperative radiotherapy. The 5-year actuarial local-regional failure rate as first site of failure was 23% for radiation only versus 5% for mastectomy and post-operative radiotherapy (p = .07). The response to chemotherapy did not reliably predict local-regional control. Both relapse-free survival and overall survival were significantly better for IIIA versus IIIB patients; stratification by repeat biopsy did not however, significantly affect either relapse-free or overall survival.

Intensive combined modality therapy of small round cell and undifferentiated sarcomas in children and young adults: local control and patterns of failure.

Seventy-five patients (ages 4-35 years) with the following small round cell tumors and undifferentiated sarcoma were treated at the National Cancer Institute: Ewing's sarcoma (n = 32), peripheral neuroepithelioma (n = 14), rhabdomyosarcoma (n = 24), undifferentiated sarcoma (n = 5). Most patients had poor prognostic features including 36 (48%) with metastatic disease, and 42 (56%) with central (truncal) tumors (22 in the pelvis). Treatment included 5 cycles of intensive induction chemotherapy with vincristine, cyclophosphamide and adriamycin, plus aggressive local radiation therapy using simulation and computerized treatment planning for all patients. Thereafter, complete clinical responses were consolidated with intensive chemotherapy, total body irradiation and autologous bone marrow transplantation. There were three local only failures, 10 local plus distant failures, 36 distant only failures, 3 treatment-related deaths, and one intercurrent death. Overall actuarial survival and event-free survival at 4 years are 49 and 29%, respectively. Actuarial freedom from local progression was seen in 74% of patients at 4 years, quite remarkable considering the bulk and location of most of these tumors. Without aggressive surgery, many of these high risk patients had satisfactory outcomes, but better systemic treatments are still needed.

Oncogene expression in neurofibromatosis.

To investigate the role of oncogenes in malignancies characteristic of neurofibromatosis, oncogene transcripts were quantitated in a neurofibrosarcoma and in control tissue from a patient with hereditary neurofibromatosis. Sis and N-ras were moderately hyperexpressed, raf, Blym, and erbA were slightly hyperexpressed, and abl, erbB, fes/fps, fgr, fos, mos, myb, myc, N-myc, rasHarvey, rasKirsten, ros, src, and yes were not hyperexpressed in the tumor compared to the control tissue. Although additional tumors will be assayed before conclusions are possible, it may be significant that the two oncogenes most hyperexpressed are prior suspects for a pathogenetic role in tumors of the nervous system.

Bilateral retinoblastoma with ectopic intracranial retinoblastoma: trilateral retinoblastoma.

In 11 patients, bilateral retinoblastoma presented at a mean age of 6 months and pineoblastoma at 4 years. We suggest that the hereditary multicentric retinoblastoma arose in vestigeal photoreceptors in the pineal as well as in the hypothetical retinoblasts of the retina. In certain lower animals, the pineal functions as a photoreceptor organ, resembles the retina histologically, and is described as a "third eye." Hence, the patients we describe may be considered as having "trilateral retinoblastoma." Two possible variants of this entity were also noted: (1) three children without retinoblastoma with rosettes and photoreceptor differentiation characteristic of retinoblastoma, and (2) three additional cases involving children who presented with retinoblastoma-like tumors in the suprasellar or parasellar region 2 to 6 months before the discovery of intraocular retinoblastoma. These observations suggest that the retinoblastoma gene confers a previously unappreciated susceptibility to a narrow spectrum of neuroblastic tumors, which usually present in the retina but which can also occur ectopically.

[Adrenal fetus in fetus. A case shown by prenatal echography. Review of the literature]. / Foetus in foetu surrénalien: un cas évoqué par l'échographie prénatale. Revue de la littérature.

The authors report the first case of fetus in fetu situated in the adrenal gland where the diagnosis was suggested by prenatal ultrasound. The anatomo-pathology, the aetiology, the antenatal ultrasound picture and the treatment of this abnormality of embryonic development are described.

[An unusual foreign body in the esophagus]. / Observation d'un corps étranger inhabituel de l'oesophage.

This is a case of oesophageal penetration by dental prosthesis probably brought on by alcoholism. No other classical complication occurred for three weeks. It was increasing dysphagia that led the patient to hospital. Endoscopy revealed an unfamiliar object and its nature, but did not enable it to be extracted. The object was taken out afterwards by cervicotomy.

US cancer incidence and mortality in the first year of life.

Based on the Third National Cancer Survey (1969 to 1971), the incidence of malignant neoplasms in the United States was 183.4 per million live births per year in infants younger than 1 year and 36.5 in newborns younger than 29 days. In both age groups, neuroblastoma was the most commonly diagnosed neoplasm. Overall, cancer incidence in infants younger than 1 year was almost 3.5 times greater than mortality determined from US death certificates from 1960 to 1969. For individual tumor types, the ratio between incidence and mortality varied between 159 for retinoblastoma and 1.5 for leukemia largely reflecting relative differences in survival due to treatment.

Neurofibromatosis and childhood leukemia.

Twelve new cases of childhood leukemia and neurofibromatosis were ascertained and evaluated in conjunction with 17 previously well-documented cases. The ratio of ALL:nonlymphocytic leukemia was 9:20, markedly different from the 4:1 ratio in children without NF. Rarer subtypes predominated: 8 CML and 8 AMML. The peculiar distribution of leukemia by cell type and the number of cases observed in the United States indicate that the risk of childhood leukemia in NF is increased. Two possible variants were noted: NF with "transient leukemia," and multiple skin xanthomas with nonlymphocytic leukemia.

Childhood malignant melanoma. Incidence and etiology.

Etiology of malignant melanoma in persons younger than 20 years of age was examined using data from two sources: medical records of 78 patients with this diagnosis at six hospitals, and information on 101 individuals included in 10 U.S. population-based SEER cancer registry areas between 1973-1976. Annual melanoma incidence rate was 3.4 per million in boys, 3.9 per million in girls, and 10-fold greater in white children than in black children. Melanoma was seven times more frequent in the second decade of life than the first. Skin was the primary site of melanoma in approximately 90% of the children in the two study series. The predominant cutaneous sites were head, neck, and trunk among boys, and arms and legs among girls. These variations by age, race, and sex suggest the etiologic role of cumulative skin exposure to sunlight, particularly in two patients with xeroderma pigmentosum. In 14 patients in the hospital series, melanoma was reported to develop within pigmented nevi that were present at birth.

Linkage analysis of neurofibromatosis (von Recklinghausen disease).

Linkage analysis of 28 genetic markers was undertaken in 108 subjects from 11 families with well-documented, classic, peripheral neurofibromatosis. Fifty-four persons were affected in one four-generation family, seven three-generation families, and three two-generation families. Lod scores were calculated using the standard LIPED programme for 49 combinations of theta male and theta female from 0.01 to 0.50. Lod scores excluded close linkage with 16 markers, including most tested on chromosome 1 and HLA on chromosome 6, and were inconclusive for 12 markers, including the secretor locus, closely linked to myotonic dystrophy. Analysis of five informative families resulted in a lod score of +2.2 for close linkage with GC on chromosome 4. However, the lod score for GC in the one additional informative family was negative, so that the final interpolated maximum was Z = 0.89 for theta male = 0.03, theta female = 0.28. Further studies are needed to evaluate this suggestion of linkage and possible genetic heterogeneity.