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Background: This study evaluated the need for surveillance imaging in early-stage classic Hodgkin lymphoma (cHL) after planned combined-modality therapy (CMT)., Methods: Primary early-stage cHL patients who underwent CMT were included. Positron emission tomography (PET)/computed tomography (CT), CT, or both were performed at the initial staging, during or after chemotherapy, and for at least 2 years during follow-up. Imaging studies and medical records were reviewed to determine if and when relapse had occurred. Radiation doses and costs were also calculated from follow-up imaging., Results: The study included 78 patients with a median follow-up of 46 months; 85% of the patients had stage II disease (32% with bulky disease). Four of 77 interim PET scans were positive; none of these patients relapsed during follow-up, which ranged from 24 to 80 months. After a total of 466 follow-up imaging studies (91% with CT and 9% with PET/CT), no cHL relapse was detected. Eleven abnormal findings were noted on surveillance imaging: 9 were false-positives, and 2 were second primary malignancies. The average cumulative dose per patient from follow-up imaging was 107 mSv, which translated into an estimated lifetime excess cancer risk of 0.5%; the estimated total costs were $296,817 according to Medicare reimbursements., Conclusions: Surveillance imaging with either CT or PET/CT can be omitted safely for early-stage cHL treated with a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine and radiation therapy because the risk of relapse is extremely low. This observation also applies to patients with bulky disease. The elimination of surveillance imaging will also reduce healthcare expenses and cumulative radiation doses in these predominantly young patients., (© 2015 American Cancer Society.)

Background: Patients with early-stage, nonbulky classic Hodgkin lymphoma (cHL) undergo intensive posttreatment radiologic surveillance despite having a low risk of disease recurrence. The current study attempted to evaluate the risk of disease recurrence and the value of radiologic surveillance in patients treated with the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone who achieved a complete remission (CR) as noted on posttreatment positron emission tomography (PET)., Methods: Forty-seven patients who underwent therapy with interim and/or posttreatment PET scans were evaluated for disease recurrence during ≥ 24 months of follow-up. Their presenting characteristics and imaging results were assessed and interpreted in relation to clinical outcome., Results: All 47 patients were eligible for analysis. The majority of patients were female (35 patients) with a median age of 28 years (range, 17 years-65 years.). The nodular sclerosing subtype was the predominant histology (41 patients). A total of 34 patients were staged with IIA disease, 6 with IA disease, 6 with IIB disease, and 1 with IIEA disease (lung) (according to Cotswolds modification of the Ann Arbor staging system). All patients completed 6 cycles of planned ABVD therapy and achieved a CR. Two had a positive PET scan (1 interim scan and 1 posttreatment scan); both were biopsy-proven sarcoidosis. Two patients developed disease recurrence at 7 months and 24 months, respectively, after negative interim and posttreatment imaging. One case of recurrence was identified through surveillance imaging and the other was identified simultaneously by the patient and surveillance scan. A total of 45 patients experienced a durable CR; 21 had additional unscheduled imaging/workup during surveillance to investigate symptoms or imaging signs of concern., Conclusions: Because of a low risk of disease recurrence, posttreatment radiologic surveillance appears to be unnecessary in patients with early-stage, nonbulky (CD20 negative) cHL who achieve a PET-detected CR with the ABVD combination alone. This will reduce cumulative radiation exposure and health care costs in a predominantly young patient population., (Copyright © 2012 American Cancer Society.)

Background: The objective of this study was to document the natural history of second lung carcinomas, common second tumors that arise in survivors of Hodgkin disease (HD)., Methods: The data bases of the Memorial Sloan-Kettering Cancer Center were searched to retrieve those patients who were listed with a diagnosis of both lung carcinoma and HD. Information was extracted regarding their HD (including age at diagnosis and treatment received) and their lung carcinoma (including smoking history, latency from HD, histology, disease stage, treatment received, treatment response, and survival)., Results: Twenty-one lung carcinomas were diagnosed in 19 patients, with a median latency of 13 years from the time of diagnosis of HD. Only five patients underwent complete resection, and four patients were alive and disease free at the last follow-up. In contrast, the median survival of 14 patients with unresectable disease was 3 months. No major objective responses were documented after chemotherapy. Poor performance status and prior thoracic radiotherapy limited treatment in patients with advanced disease. All patients had either received radiotherapy to the chest for HD or had a history of smoking; 74% of patients had both risk factors for the development of lung carcinoma., Conclusions: In patients with a history of HD, survival after the development of lung carcinoma is poor. Because surgical resection can lead to long-term survival, early detection is crucial. HD survivors, especially those with a history of smoking, should undergo careful surveillance for second primary lung carcinomas and other diseases. Patients who are diagnosed with HD should abstain from smoking. Physicians should assess specifically the smoking status of all HD patients and prescribe a smoking cessation program., (Copyright 2002 American Cancer Society.)

Cisplatin and dacarbazine are used widely in the treatment of metastatic melanoma. To evaluate high-dose cisplatin and dacarbazine, 32 patients with metastatic melanoma were treated with cisplatin 50 mg/m2 and dacarbazine 350 mg/m2 daily for three days repeated at 28-day intervals. Their median age was 43.5 years (range, 25 to 73 years), and their median Karnofsky performance status was 80% (range, 70% to 100%). Measurable and evaluable disease sites (number of patients) included lymph nodes (22), lung (17), soft tissue (16), liver (13), bone (seven), spleen (four), adrenal gland (three), skin (three), and other sites (five). Patients received a median of two cycles of therapy (range, one to eight cycles). Thirty patients were evaluable for response. No complete responses were observed. Five patients had a partial response (17%; 95% confidence interval, 3% to 30%) for 16+, 12+, 7, 6.5, and 3 months. Responding sites of disease included lymph nodes (five of 22), lung (three of 17), and soft tissue (two of 16). Hematologic toxicity (Grade greater than or equal to 3) included neutropenia (16 of 32 patients, 30 of 90 cycles), thrombocytopenia (eight of 32 patients, 12 of 90 cycles), and anemia (five patients). Nine episodes of neutropenia and fever were seen in four patients; two had bacteremia. Nonhematologic toxicity (Grade greater than or equal to 3) included hypotension (two patients), nausea and vomiting (four), neuropathy (two), ototoxicity (four), and hypomagnesemia (nine). The low objective response rate and severe toxicity of this regimen preclude its standard use in patients with metastatic melanoma. A review of cisplatin-based therapy in metastatic melanoma suggests that there is no dose-response relationship. The use of high-dose cisplatin (greater than 100 mg/m2) in the treatment of metastatic melanoma is not recommended.

The combination of cisplatin plus dacarbazine (DTIC) is active in metastatic melanoma with response rates reported between 10% and 55%. To optimize this regimen, a Phase II study was conducted employing a dose intensity of cisplatin higher than previously reported. Twenty-two patients were treated. Eight patients received cisplatin 100 mg/m2 on days 1 and 8 combined with DTIC 300 mg/m2 on days 1, 2, 8 and 9 (regimen A). Because of excessive toxicity, the protocol was modified so that cisplatin was given at 50 mg/m2 per day and DTIC 350 mg/m2 per day on days 1 through 3 (regimen B). The overall response rate was 32% and consisted of four partial and three complete responses (CR). The median duration of response was 6 months. Two of the CR remain in sustained, unmaintained remission in excess of 1.5 years. All seven patients that responded were treated on regimen B. High-dose cisplatin plus DTIC on a 3-day schedule represents an effective, well-tolerated therapy for metastatic melanoma.

Seven previously untreated patients and two previously treated patients with advanced non-Hodgkin's lymphoma (Stages III and IV) and favorable histologic subtypes had spontaneous regression of their lymphomas. Regressions were either complete or partial and were frequently durable. Six of the seven patients who had spontaneous regression of their lymphomas prior to any therapy have yet to require treatment. Seven of the nine spontaneous regressions occurred in a group of 44 patients who were followed with initial therapy deferred. Six patients had regression of their lymphomas prior to any therapy and one patient had previously received a small field of radiation therapy. Temporary spontaneous regression of lymphoma may be common in selected patients with favorable histologies and advanced disease in whom initial therapy is deferred.

Between March 1973, and December 1976, 22 patients who developed disease progression during or after MOPP therapy were treated with a new combination, B-CAVe (Bleomycin 5 mg/m2 iv days 1, 28, 35; CCNU 100 mg/m2 po day 1; adriamycin 60 mg/m2 iv day 1; and vinblastine 5 mg/m2 iv day 1). Objective responses were achieved in 17 of 22 patients (77%) and 11 of 22 responses were complete (50%). The actuarial survival for all patients is 16.4 months. For complete responders the median is 24 months with 2 complete responders dead without evidence of Hodgkin's Disease. Median relapse free survival for complete responders has not been reached at 35+ months while that for partial responders is 14 months. Significant adriamycin cardiotoxicity was encountered in two patients. There were no life threatening bacterial infections during B-CAVe. Two patients died of Pneumocystis carinii several months after cessation of therapy. B-CAVe is effective in the therapy of advanced Hodgkin's disease after MOPP failure, and this regimen is comparable to other previously reported MOPP salvage combinations.

Between February 12, 1968 and August 17, 1977, 473 consecutive patients with Hodgkin's disease were entered into protocol studies at Stanford University Medical Center (SUMC). 242 of these 473 patients were pathological Stage I or II; 223 patients had disease above the diaphragm and 19 patients had disease confined below the diaphragm. When compared to patients with disease above the diaphragm, patients with Hodgkin's disease below the diaphragm were more frequently male (74% vs. 53%, p = 0.14), were on the average older (40 vs. 27, p less than .005) and more frequently had the histologic subtype of mixed cellularity (32% vs. 12%, p = .04). There was no difference in either survival or relapse-free survival between patients with Hodgkin's disease above the diaphragm and patients with disease below the diaphragm receiving similar treatment plans.

From June 19, 1975 to December 22, 1976, twenty-seven patients with advanced Hodgkin's disease who failed MOPP (nitrogen mustard, vincristine, procarbazine and prednisone) were treated with adriamycin, bleomycin, vinblastine, and imidazole carboxamide, (ABVD). Complete response (CR) was achieved in 22% of patients and partial response was achieved in 15%. No response was observed in 63% of patients. With a median duration of follow-up for CR patients of only 10.5 months, two of the six CR patients have already relapsed. In this series of patients ABVD was not an effective curative regimen for patients with Hodgkin's disease who have failed MOPP.

A total of 440 previously untreated patients with Hodgkin's disease have been treated on randomized clinical trials at Stanford University, testing the value of combined modality therapy. A group of 244 patients with stages I, II and III were treated between 1968 with radiotherapy alone or combined with adjuvant MOPP chemotherapy. The adjuvant MOPP significantly improves the initial freedom from relapse (FFR) duration but improvement in survival is only minimal and not yet significant. The ability to induce a second durable remission after initial treatment failure results in freedom from second relapse rates (FF2dR) which more closely parallel survival figures than FFR. Adjuvant MOPP cannot yet be recommended as a routine adjuvant in the radiation maanagement of Hodgkin's disease. A pilot trial of the role of radiation therapy in the chemotherapy management of stage IV patients does not indicate an advantage of the irradiation. Preliminary analyses of new treatment programs in 163 patients with all stages of disease treated between 1974--1977 indicate improved survival and FFR rates, the majority of patients receiving combined modality therapy. Only three patients have died and nine patients have relapsed during the three year period of these new trials.

Twenty-seven evaluable patients with refractory, metastatic breast carcinoma were treated with Adriamycin (doxorubicin) 30 mg/m2 and vinblastine 6 mg/m2 intravenously on days 1 and 28 every 8 weeks, and mitomycin C 10 mg/m2 intravenously on day 1 every 8 weeks (AVM). There were three complete and six partial responses for a total response rate of 33%. In addition, 2 patients had minimal responses, and 10 patients achieved disease stabilization. Median time to disease progression for responders was 116 days (range, 49-812+ days). Drug toxicity was tolerable: 12 patients (44%) experienced significant bone marrow suppression. There were no drug-related deaths. Although AVM appears to be an active drug combination in heavily pretreated patients with metastatic breast carcinoma, the contribution of vinblastine and mitomycin C to single agent Adriamycin in previously treated patients is not clear from this study.

From July 1971 to July 1974, 58 patients with advanced non-Hodgkin's lymphomas were treated with cyclophosphamide, vincristine, prednisone (CVP) at Stanford Medical Center. Utilizing the histopathologic criteria of Rappaport el al., response to CVP was found to be significantly better in the nodular (96.6%) and the diffuse lymphocytic (100%) histologies as compared to the diffuse nonlymphocytic lymphomas (47.6%). A pathologically documented complete remission was obtained in 33.9% of patients and all but two remain disease free for periods of 2-28 months. Concurrent bleomycin was administered to 17 patients during CVP therapy and no improvement in response or median survival was noted. Prior radiation therapy delivered to 21 patients did not adversely affect their response to CVP or their survival. Splenectomy in 17 patients prior to CVP did not improve hematologic tolerance to chemotherapy except in those patients with prior radiation therapy, and there was no improvement in response to CVP or survival. CVP is effective in achieving complete remissions and extended disease-free survivals in advanced non-Hodgkin's lymphomas; both a nodular architecture and a diffuse lymphocytic histology are positive determinants for response to chemotherapy and improved median survival.

Twenty-three patients with diffuse histiocytic lymphoma who had not had prior chemotherapy were treated with CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone). Sixteen of these patients had previously been treated with radiation therapy. Nine of these 23 patients had a pathologically documented complete response at the conclusion of CHOP with an overall complete response rate of 39%. In patients whose disease was confined to lymph nodes, the complete response rate was 7 of 8 or 88%, while in patients with stage IV disease, only 2 of 15 or 13% had complete responses. Although prior radiation therapy could not be demonstrated to be an adverse prognostic factor in this small series, it could have accounted for the low overall complete response rate noted. Complete response in this series was well sustained with an actuarial relapse-free survival of 75% and an actuarial survival of 89% at two years. No complete responses occurred in five patients who had received prior chemotherapy.