Charles H. Diggs

Radiation-Related Thyroid Dysfunction: Implications for the Treatment of Hodgkin's Disease

Thyroid-stimulating hormone (TSH) and thyroxine (T/sub 4/) were measured in sera from 214 patients with Hodgkins disease. The literature was reviewed for patients with lymphoma or head and neck carcinoma who had received prior radiation therapy that encompassed the thyroid. Among 169 patients who had been treated with mantle radiation therapy at our center, 112 (66%) had evidence of thyroid dysfunction, including 43 with depressed T/sub 4/ levels. Among 45 who did not receive mantle irradiation, only three had evidence of dysfunction and none of these had T/sub 4/ depression. Thyroid dysfunction developed slowly, with less than 15% of patients tested during the first year showing dysfunction and the maximum of 66% reached at about 6 years. This entity is very common in lymphoma patients yet often is overlooked except in instances of specific thyroid function evaluation for research. A substantial proportion of patients with head and neck carcinoma develops thyroid dysfunction after irradiation, especially if therapy includes hemithyroidectomy. Serum TSH measurement every 6 months for at least 5 to 6 years after irradiation will detect early thyroid dysfunction. All patients with elevated serum TSH should be treated with sodium levothyroxine, regardless of whether they are clinically hypothyroid.

Combined modality treatment of Hodgkin's disease confined to lymph nodes: Results eight years later

Eighty-seven patients with newly diagnosed Hodgkins disease, pathologic stages IA, IIA, IIB and IIIA, were assigned at random to receive either extended field radiotherapy alone or that therapy followed by six cycles of MOPP (nitrogen mustard, Oncovin, procarbazine, prednisone) chemotherapy. Patients were entered into the study from January 1970 to January 1974. Patients were followed for a median of 69 + months from the end of all treatments. Patients whose disease was less than stage IIIA had a 31 per cent relapse rate with radiotherapy alone compared to a 6 per cent relapse rate with combined modality treatment (P = 0.04). No deaths from Hodgkins disease have occurred in patients who received combined modality therapy, whereas 24 per cent of the patients who received radiotherapy alone have died with active disease. However, three patients with stage IIIA disease who were treated with both modalities have died from other causes (myocardial infarction, adenocarcinoma of lung, acute leukemia). Combined modality therapy of patients with early Hodgkins disease may be superior to radiotherapy alone, especially for certain subgroups of patients discussed in detail.

Infections During Intensive Chemotherapy for Non-Hodgkin's Lymphoma

Records of 133 infections occurring in 73 of 125 patients with late-stage non-Hodgkins lymphoma on intensive chemotherapy programs for a median of 23 months were reviewed. Granulocytopenia, usually related to chemotherapy, was the major predisposing factor, association with 51% of infections. The incidence of infection in chemotherapy courses associated with less than 500 granulocytes/microL was higher than those with 500 or more granulocytes/microL (p = 0.0004). Splenectomized patients tended to have a higher incidence of chemotherapy courses with an infection (p = 0.06); marrow involvement was not a significant predisposing factor to infection. The commonest sites of infection were lung, skin, and alimentary canal. Gram-negative organisms and Staphylococcus aureus caused 83% of documented infections; Pseudomonas aeruginosa was the major cause of pneumonia and bacteremia; and herpes zoster and fungi each caused only 3% of infections. Other infections associated with impaired cellular or humoral immunity were uncommon. Poor prognosis was associated with infections in granulocytopenic patients with stable or falling granulocyte counts, infection at multiple sites, and bacteremia, especially polymicrobial bacteremia.

Cyclophosphamide, vinblastine, procarbazine and prednisone with CCNU and vinblastine maintenance for advanced Hodgkin's disease.

Fifty patients with advanced Hodgkins disease were treated with a combination of cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP) in a 21‐day cyclic regimen. Thirty‐one patients (62%) achieved a pathologically documented complete remission (CR). Of the 23 previously untreated patients, 13 obtained CR. Twenty‐seven patients had been previously treated and 15/19 (79%) of those with prior major radiation therapy and 3/8 (37.5%) of those who had received both irradiation and chemotherapy achieved CR. Sixteen of the patients who attained CR received maintenance therapy with monthly alternating CCNU and vinblastine but as of this report, neither remission duration nor survival is significantly prolonged when compared to the 14 patients followed in remission on no therapy. Patients who received more than six courses of induction therapy (median 9.5, range 8–12) have had significantly fewer relapses and longer remissions than have those patients who received only six courses of therapy. It is concluded that: 1) CVPP is an effective regimen at inducing CR in patients with advanced Hodgkins disease and has less gastrointestinal and neurologic toxicity than MOPP; 2) maintenance therapy with CCNU and vinblastine to date has not been beneficial; and 3) greater than six courses of induction chemotherapy prolongs remission duration and is associated with fewer disease relapses.

Anatomic Substages of Stage III-A Hodgkin's Disease: A Collaborative Study

The clinical significance of anatomic substage was assessed in 130 patients with Hodgkins disease in pathologic stage III-A: stage III1-A includes involvement of spleen, or splenic, celiac, or portal nodes, or any combination of these; stage III2-A includes involvement of para-aortic, iliac, or mesenteric nodes, with or without upper abdominal involvement. Median follow-up was 58 months. Both 5-year disease-free survival, 74% versus 46%, and 5-year survival, 94% versus 65%, were better (P less than 0.001) in stage III1-A than in stage III2-A. In stage III1-A, 5-year disease-free survival was better in patients receiving radiotherapy and chemotherapy than in patients receiving radiotherapy alone as initial treatment, 96% versus 63%, P less than 0.003; however, 5-year survival rates in P = 0.22. For stage III2-A, both 5-year disease-free survival, 76% versus 32%, P less than 0.001, and 5-year survival, 84% versus 56%, P less than 0.03, were superior with radiotherapy-chemotherapy. Consideration of anatomic substage may aid therapeutic planning for stage III Hodgkins disease.

Adriamycin therapy in advanced mycosis fungoides

Thirteen patients with advanced mycosis fungoides received induction therapy with Adriamycin, 60/m2 I.V. repeated at 21‐day intervals. Ten patients had extensive skin tumors; all patients had lymph node enlargement with mycosis fungoides involvement in eight; four patients had biopsy‐proven visceral involvement. Only two patients had received no prior therapy. The overall response rate with Adriamycin therapy was 85% with three patients (23%) achieving a biopsy‐proven complete remission and five patients (39%) partial remissions. The median number of courses to maximum response was two (range two to four). The principle toxicity was myelosuppression, but this was not severe and the entire group received more than 90% of the intended doses of Adriamycin. One patient developed probable Adriamycin cariotoxicity. Maintenance therapy for patients achieving a remission was methotrexate 15 mg/m2 I.M. twice weekly and cyclophosphamide 750 mg/m2 I.V. every 21 days. The median duration of complete remission was 32+ weeks (range 16+ −40+ weeks) while the median duration of partial remission was 18 weeks (range 8–111+ weeks). Adriamycin has proven to be an effective induction agent in the treatment of advanced mycosis fungoides and its incorporation into combination chemotherapy regimens is warranted.

Fungal infection of muscle in acute leukemia

A patient with acute lymphoblastic leukemia and granulocytopenia developed fever and diffuse muscle pain and weakness while under therapy. Blood cultures grew Candida Krusei and autopsy showed diffuse muscle fungal infestation.

Causes of death in patients with non-Hodgkin's lYMPHOMA

The causes of death and postmortem findings in patients treated for non‐Hodgkins lymphoma at a single institution over a 13‐year period were reviewed. Postmortem examination (70% of the entire sample) revealed evidence of lymphoma in 67 of 80 patients. The most frequent extranodal sites of involvement were the respiratory tract, bone marrow, liver, kidney, and gastrointestinal tract in that order. The most common cause of death was infection (33% of cases). Predisposing factors for infection included the underlying disease, (i.e., lymphomatous infiltration of organ systems) and granulocytopenia secondary to combination chemotherapy. Other causes of death included hemorrhage and respiratory failure secondary to lymphomatous infiltration of the lung. Despite advances in therapy and supportive care of patients with non‐Hodgkins lymphoma, many patients still die of this disease or of sequelae related to its treatment.

Treatment of advanced untreated Hodgkin's disease with SCAB—an alternative to MOPP

SCAB chemotherapy streptozocin (streptozotocin) lomustine (CCNU), doxorubicin hydrochloride (Adriamycin), and bleomycin sulfate was given in monthly courses to 20 patients with Stages IIIB, IVA, and IVB previously untreated Hodgkins disease. Complete remissions were obtained in 15 (75%) of these patients, and partial remissions in two others. Toxicity of this program was acceptable. Although this study was not a direct comparison with MOPP, SCAB would appear to be at least as effective as MOPP and offers a reasonable alternative treatment program for the patient with advanced stage, previously untreated Hodgkins disease.

Small cell carcinoma of the lung. Treatment in the community

The results of nonprotocol treatment of 232 patients with small cell lung cancer seen by a group of community‐based medical oncologists over a 13‐year period were evaluated. Factors associated with improved survival also were assessed. The following patient characteristics significantly improved survival: limited stage of disease at diagnosis, treatment of extensive (but not limited) disease with regimens including etoposide and cisplatin, tumor resection, age younger than 70 years, radiation therapy to the chest, and female sex (extensive disease only). Comparison of the data from this study with published results of protocol studies showed similar outcomes.