Larry E. Kun

A randomized study of adjuvant chemotherapy for cancer of the upper aerodigestive tract

A prospective, randomized trial of induction chemotherapy in advanced squamous cell carcinomas of the upper aerodigestive tract (UAD) was conducted between July 1979 and September 1982. Eighty-three patients with locally advanced Stage III-IV tumors received standard treatment (STD RX; defined as preoperative irradiation and radical excision or irradiation alone), or induction chemotherapy (CTX) followed by STD RX. Chemotherapy consisted of two cycles of bleomycin (30 units/day by continuous infusions Days 1-4), cyclophosphamide (200 mg/m2 IV Days 1-5), methotrexate (30 mg/m2 Days 1 + 5), and 5-fluorouracil (400 mg/m2 IV Days 1-5). Response to CTX was complete in 2 and partial (greater than 50% reduction) in 27; the overall response rate was 68%. Tumor clearance was documented in 30/40 STD RX patients at completion of irradiation and/or surgery and in 24/43 CTX patients (17/29 responders, 7/14 non-responders). Freedom from local-regional disease was noted at 2 years in 53% STD RX and 35% CTX patients (p less than .06). CTX patients had a higher proportion of local-regional persistence and recurrence. The difference was apparent only in the subset of patients treated with primary irradiation; local-regional control following irradiation and surgery was equal in STD RX and CTX groups. Survival at 2 years was 43% STD RX and 31% CTX. Disease-free survival in those with clearance was 64% STD RX and 59% CTX. Induction chemotherapy did not improve tumor clearance or survival in this series. Caution regarding local-regional control with CTX and primary irradiation is noted.

Randomized Study of Adjuvant Chemotherapy for Head and Neck Cancer

The ability of surgery and radiotherapy to control advanced squamous cell carcinoma of the head and neck has reached its maximal potential. We initiated a randomized, prospective, stratified study of adjuvant chemotherapy. Patients with stage II disease of the pyrlform sinus and stage III and IV disease of the oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, and paranasal sinuses were eligible. Patients were randomized to receive either standard therapy alone or two courses of 5-fluorouracil (B-CMF) chemotherapy prior to and two courses after the completion of standard therapy. Standard therapy consisted of preoperative irradiation followed by radical surgery. Of 133 patients with advanced disease, 83 were included In the study—43 In the chemotherapy group and 40 In the control group. Rates of residual and recurrent disease, as well as distant metastases, were similar for the two groups. The survival rates of patients without persistent disease at the end of treatment showed no significant difference for the two groups. The study has been discontinued because statistical analysis Indicated that the addition of more patients would not materially Increase the statistical significance of the study.

Hepatopathy following irradiation and adriamycin.

This report describes two cases of hepatopathy following irradiation and adriamycin at doses and volumes of irradiation ordinarily considered within the tolerance of hepatic function. In one case fatal hepatopathy followed 2400 rad/17 fractions/28 days to the entire liver with preceding and concurrent adriamycin. In the second case moderate clinical changes occurred after treatment in which much of the right lobe of the liver was shielded following 2500 rad/23 fractions/32 days with adriamycin administered before, during, and after irradiation. The locally enhancing effects of adriamycin on hepatic tolerance to irradiation are discussed.

Primary cerebral germinoma and ventriculoperitoneal shunt metastasis

A case of peritoneal metastasis via a ventriculoperitoneal shunt 14 months following biopsy and irradiation of an intracerebral germinoma is presented. Metastatic abdominal disease has been controlled at 32 months postmetastatic diagnosis by abdominal irradiation and systemic chemotherapy. The occurrence of ventriculoperitoneal shunt metastases and control of extracranial metastases from intracerebral germinomas are discussed.

Neuropsychological sequelae of childhood brain tumors: A review

Although children with brain tumors account for 20% of all pediatric cancer and comprise a theoretically important population for the study of brain‐behavior relationships, surprisingly few neuropsychological investigations have been forthcoming. Evidence regarding the effects of hydrocephalus, age at diagnosis, extent of irradiation treatment, and tumor location on the subsequent neuropsychological status of survivors is reviewed. Failure to adequately analyze these variables and their potential interactions, equivocal findings across studies, a lack of sophistication in neuropsychological assessment and study design, and conclusions based upon small and oftentimes heterogenous samples are prevalent problems. Although it appears that young children with supratentorial tumors who receive cranial irradiation are at highest risk for intellectual, academic, and emotional dysfunction, further research is sorely needed to define the relationship between disease‐ and treatment‐related variables and subsequent n...

Stage III nodular lymphoreticular tumors (non-Hodgkin's lymphoma): results of central lymphatic irradiation.

Since 1969, 29 previously untreated patients with Stage III nodular malignant lymphoreticular (MLT) have received total central lymphatic (TCL) irradiation. The volume irradiated included the entire abdomen, Waldeyers ring, and preauricular nodes in addition to the usual regions encompassed by total nodal irradiation. Doses of 2000–3000 rads in three to six weeks were delivered to the nodal regions, liver, and spleen; fraction sizes ranged from 100 to 180 rads. Patients have been followed from one to ten years (median six years). The actuarial survival is 78% at five years, and the disease‐free survival is 61%. There is no difference in disease‐free survival of the patients with poorly differentiated lymphocytic vs. those with “histiocytic” or mixed cytology. Men and women had disease‐free survivals of 82% and 43%, respectively. The long‐term follow‐up of these patients indicates that prolonged disease‐free intervals are common after TCL irradiation, and some patients may be cured.

Local control of intrathoracic disease with chemotherapy and role of prophylactic cranial irradiation in small‐cell carcinoma of the lung

Between 1978 and 1979, 39 consecutive patients at the Medical College of Wisconsin were seen with small‐cell carcinoma of the lung; of these, 31 were treated with chemotherapy and prophylactic CNS irradiation (2500 rad/10 fractions) and were evaluable after 22 month median follow‐up. The intra‐thoracic primary was not irradiated unless there was no response to chemotherapy or subsequent recurrence. Of the 31 patients, 12 had limited disease (LD) and 19 had extensive disease (ED). Twenty, including all the patients with LD, had a complete response, eight had a partial response, and three were nonresponders. Of 24 patients with complete response at the primary site, 20 subsequently displayed local failure of the intrathoracic primary tumor, most developing disseminated extrathoracic disease simultaneously with or shortly after primary failure. The median survival time (MST) of the evaluable group was ten months with an actuarial one‐year survival of 39%. Patients with LD had a median remission duration of 13 months and a MST of 16 months. Three patients are still alive with no evidence of disease at 14,20, and 27 months. Of 26 patients receiving prophylactic cranial irradiation, all are free of CNS relapse. Chemotherapy alone appears insufficient to permanently control the bulky intrathoracic tumor, leading to the use of “consolidation” irradiation of moderate dose (3750 rad/15 fractions) to follow chemotherapy. Prophylactic CNS irradiation should be used routinely.

The role of thoracic and cranial irradiation for small cell carcinoma of the lung.

Since 1974, 120 previously untreated patients with small cell carcinoma of the lung seen in Therapeutic Radiology at The Medical College of Wisconsin have been entered into one of 4 successive studies. Study I used thoracic irradiation (TI) alone (4500-6000 rad in 3-6 weeks) with chemotherapy at progression. Study II randomized patients with limited disease to TI (3000 rad in 2 weeks) plus either cyclophosphamide, doxorubicin, vincristine (CAV) or total body irradiation (TBI); patients with extensive disease received TI + CAV. Study III employed prophylactic cranial irradiation (PCI) plus CAV and withheld TI unless there was incomplete response or recurrence. Of 93 evaluable patients from the first three studies, 55 had limited and 38 extensive disease. Study I (37 patients) showed a 62% complete response (CR) rate; 43% failed in the chest, 14% had brain metastases, and the median survival was only 22 weeks in spite of a preponderance of limited disease patients. Study II (27 patients) showed a CR of 59%; 30% had brain metastases and the median survival was 48 weeks. Study II patients (29) had a 69% rate; 72% failed in the chest, 4% with PCI developed brain metastases, and the median survival was 50 weeks. In March, 1979, Study IV was initiated; patients receive PCI (2500 rad in 2 weeks) plus high dose CAV, methotrexate and leucovorin. After 6 cycles, consolidation TI (3750 rad in 3 weeks) is given to patients with complete response. Preliminary results with 27 patients treated on this study show a 67% CR rate, a 41% chest failure rate (but only 11% for the patients who received thoracic irradiation) and no intracranial failures, but a 13% extracranial CNS failure rate. PCI, TI and spinal irradiation may be necessary to maximize the probability of long term disease free survival.

Spinal cord metastasis in small cell carcinoma of the lung

Among 50 patients with small cell bronchogenic carcinoma who were placed on a protocol of combined chemotherapy and radiation therapy, seven patients developed recurrence in the spinal cord. Five cases terminated in paraplegia and death. One patient with pontine recurrence recovered with local radiation therapy. One patient, diagnosed early, responded to local radiation therapy and is ambulatory. Methods of diagnosis were myelogram, computerized axial tomography, cerebro spinal fluid, chemistry and cytologies. The poor prognosis and the difficulty of diagnosis suggest that we should evaluate prophylactic therapy of the entire cranio-spinal axis.

Cranial irradiation in acute leukemia: dose estimate in the lens.

Abstract Cranial irradiation for subclinical arachnoid infiltration is standard treatment in childhood acute lymphocytic leukemia. The incidental dose received by the ocular lens is of potential importance since these children evidence a significant long-term survival rate. Comparison of the lens dose using 6 MV and 4 MV photon beams and a cobalt unit is presented in terms of ion chamber measurements in a water phantom and thermo-luminescent dosimetry (TLD) measurements in a head phantom. TLD measurements on patients treated for acute lymphocytic leukemia (ALL) are examined and used to estimate the dose to the lens. It is demonstrated that the dose to the lens depends strongly on the choice of field margin and on the daily patient set-up. However, using parallel opposed beams in a clinically determined optimal set-up, the dose to the lens is approximately 20–30% of the midline central axis dose. By angling the treatment head to eliminate the geometrical divergence of the beam, it is possible to reduce the lens dose to approximately 15% of the midline dose.