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Purpose: NRG Oncology RTOG 9704 was the first adjuvant trial to validate the prognostic value of postresection CA19-9 levels for survival in patients with pancreatic carcinoma. The data resulting from this study also provide information about predictors of recurrence that may be used to tailor individualized management in this disease setting. This secondary analysis assessed the prognostic value of postresection CA19-9 and surgical margin status (SMS) in predicting patterns of disease recurrence. Methods and materials: This multicenter cooperative trial included participants who were enrolled as patients at oncology treatment sites in the United States and Canada. The study included 451 patients analyzable for SMS, of whom 385 were eligible for postresection CA19-9 analysis. Postresection CA19-9 was analyzed at cut points of 90, 180, and continuously. Patterns of disease recurrence included local/regional recurrence (LRR) and distant failure (DF). Multivariable analyses included treatment, tumor size, and nodal status. To adjust for multiple comparisons, a P value of ≤ .01 was considered statistically significant and > .01 to ≤ .05 to be a trend. Results: For CA19-9, 132 (34%) patients were Lewis antigen–negative (no CA19-9 expression), 200 (52%) had levels

Locally advanced unresectable pancreatic adenocarcinoma is characterized by poor survival despite chemotherapy and conventional radiation therapy (RT). Recent advances in real-time image-guided stereotactic radiosurgery (SRS) have made it possible to treat these cancers in two to four fractions followed by systemic chemotherapy.The aims of this study includes the following: (1) obtain local control of the disease; (2) improve the survival of these unresectable patients; (3) evaluate the toxicity of SRS; and (4) report results of the largest series from a single center.Pancreatic SRS involves delivery of high doses of accurately targeted radiation given non-invasively in two to four fractions. We treated 85 consecutive patients with locally advanced and recurrent pancreatic adenocarcinoma from February 2004 to November 2009. Age range: 36-88 years, median 66 years; sex: 50 males, 35 females; race: 79 Caucasian, five African American, one Asian; histology: 80 adenocarcinoma, three islet cell, two other. Pre-SRS staging: T(3-4) 85; N(+) 16, N(x) 57, N(0) 12; M(0) 64, M(1) 21. All patients were unresectable at the time of SRS. Seventy-one had no prior surgical resection, and 14 had local recurrence after prior surgical resection. Twenty-nine patients had progression of disease after prior conventional RT. Location of the tumor: head, 57; body and tail, 28. Pre-SRS chemotherapy was given in 48 patients. All patients received gemcitabine-based chemotherapy regimen after SRS. Median tumor volume was 60 cm(3). PET/CT scans done in 55 patients were positive in 52 and negative in three patients. Average maximum standard uptake value was 6.9. Pain score on a scale of 1-10 was: 0-3 in 54, 4-7 in 18, and 8-10 in 13 patients. SRS doses ranged from 15 to 30 Gy with a mean dose of 25.5 Gy delivered in 3 days divided in equal fractions. Mean conformality index was 1.6, and mean isodose line was 80%.Tumor control: complete, partial, and stable disease were observed in 78 patients for the duration of 3-36 months with median of 8 months. Pain relief was noted in majority of patients lasting for 18-24 weeks. Most of the patients died of distant disease progression while their primary tumor was controlled. Overall median survival from diagnosis was 18.6 months and from SRS it was 8.65 months. For the group of 35 patients with adenocarcinoma without prior surgical resection or RT and no distant metastases, the average and 1-year survival from diagnosis was 15 months and 50%, respectively, and from SRS it was 11.15 months and 30.5%, respectively.A total of 19 (22.37%) patients developed grades III/IV GI toxicity including duodenitis, 12 (14.1%); gastritis, 11 (12.9%); diarrhea, three (3.5%); and renal failure was noted in one (1.2%). Three patient had both gastritis and duodenitis. Toxicity was significantly more prevalent in the first 40 patients compared with the last 45 patients (32.5 vs 13.9%).SRS for unresectable pancreatic carcinoma can be delivered in three fractions with minimal morbidity and a local tumor control rate of 91.7%. The survival is comparable or better than the reported results for advanced pancreatic cancer, specifically for the group of previously untreated patients with unresectable tumors. Development of distant metastases remains a significant factor.

Malignant melanoma is increasing in frequency at a rapid rate in the United States. Metastatic disease is chemoresistant with DTIC considered the most active single agent. CI-980 is a synthetic mitotic inhibitor that blocks the assembly of tubulin and microtubules. It has shown cytotoxic activity against a broad spectrum of murine and human tumor cell tines. CI-980 can cross the blood brain barrier, is effective when given orally or parenterally, and is active against multidrug resistant cell lines overexpressing P-glycoprotein. In this trial, patients with disseminated melanoma with measurable disease, SWOG performance status of 0-1, no prior chemotherapy or immunotherapy for metastatic disease, and adequate hepatic and renal function, were enrolled. Treatment with CI-980 was given by 72 h continuous i.v. infusion at a dose of 4.5 mg/m2/day, days 1-3 every 21 days. Twenty-four patients were registered on this study with no patients ineligible. They ranged in age from 33-78 with performance status of 0 in 15 patients and 1 in 9 patients. Nineteen patients had visceral disease with 12 having liver involvement. There were no confirmed responses. The overall response rate was 0% (95% CI 0%-14%). The median overall survival is eleven months (95% CI 4-14 months). The most common toxicities were hematologic and consisted of leukopenia/granulocytopenia and anemia, with nausea/vomiting and malaise/fatigue/weakness also frequent. CI-980 administered at this dose and schedule has insufficient activity in the treatment of disseminated malignant melanoma to warrant further investigation.

Angiosarcoma is a rare and aggressive tumor of the thyroid gland, mainly seen in the Alpine regions. We present such a case with literature review. We present the case of a 60-year-old man with cough, dyspnea, and hemoptysis along with slow increase in the size of his long-standing goiter. Computed tomography of the neck showed a large thyroid mass and chest imaging revealed multiple pulmonary nodules. Fine needle aspiration cytology and tru-cut biopsy of the thyroid were notable for poorly differentiated malignant cells. Diagnosis of angiosarcoma of the thyroid was made after total thyroidectomy. Patient died of continued hemoptysis and respiratory failure 3 weeks after admission. We searched the literature for previous case reports using Pubmed and Ovid. Forty-seven reported cases were identified and our case was added to make a database of 48 cases. Demographic and tumor characteristics were analyzed. Angiosarcoma was found to be more common in females and at age of 60 or above. Results were consistent with previously reported series of 14 and 17 cases from Austria. This review provides information on various characteristics angiosarcoma of the thyroid which can be used as baseline data for future reference and research studies for this cancer.

Background : The pharmacokinetics of dacarbazine (DTIC), which has been shown to be an effective therapeutic agent against metastatic melanoma, has not been extensively studied. However, to improve the clinical use of the drug, more information on the kinetics is required. Methods : A pharmacokinetic study was undertaken in six patients with melanoma of an extremity who were undergoing hyperthermic isolation perfusion with DTIC in order to understand better its clinical pharmacokinetics. Plasma was sampled from the arterial and venous lines of an extracorporeal pump during the perfusion with the systemic vein and urine sampled postperfusion. Samples were analyzed for DTIC, 2-azahypoxanthine (2-AZA), and aminoimidazole carboxamide (AIC). 99m Tc (Technetium) human serum albumin (HSA) was used in the perfusion circuit to monitor the crossover of the perfusate into the systemic circulation during the procedure. The data were analyzed using a compartmental model of sampled body compartments incorporating the isolated extremity. Results : High tissue DTIC levels were maintained throughout the perfusion, whereas in the systemic circulation, plasma DTIC concentrations, when observed, were 40-100-fold less than those in the perfusate. Almost 70% of the DTIC administered was not recovered in the perfusate after the washout of the extremity. Conclusions : High levels of DTIC can be maintained in an extremity (i.e., arm or leg) during perfusion.

Internal mandibular fixation after resection of advanced oral cavity carcinoma with mandibulectomy has a significant complication rate. We placed the Joe Hall Morris (JHM) external mandibular appliance in 29 patients undergoing mandibulectomy for advanced oral cavity carcinoma. Fourteen patients received postoperative radiation therapy (RT). Three of 29 patients (10%) had complications associated with the JHM appliance: one patient had a broken connecting bar, a second had loosening of a single pin, and a third had loss of fixation requiring complete replacement of the appliance. Complications not associated with the appliance occurred in 8 patients (28%) including mandibular exposure (1), orocutaneous fistula (2), partial flap dehiscence (4), and flap necrosis (1). Oral continence was maintained in 26 patients, and occlusion was normal in 27. The appliance was removed in 12 weeks to 6 months in all patients. The JHM appliance allows for a reliable and rapid immediate fixation of the mandible with acceptable functional and aesthetic results, and no delay or interference with postoperative radiotherapy. Since the life expectancy of these patients is short, most do not require subsequent permanent fixation after removal of the appliance.

Twenty-eight patients with inflammatory carcinoma of the breast were managed initially by induction chemotherapy consisting of 3 courses of a combination of cyclophosphamide, doxorubicin hydrochloride, and 5-fluorouracil. Twenty-two showed a partial response, and 21 underwent mastectomies. Histopathologic examination of the surgical specimens revealed no residual tumor in 2 breasts, but all 21 patients had residual metastases in their axillary lymph nodes. Postoperatively, they received the same chemotherapy. The other six patients who failed to respond to induction chemotherapy received radical radiation therapy followed by a combination chemotherapy regimen that consisted of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone. Any patient in whom chemotherapy failed during the follow-up period was treated by radiation therapy and/or a combination of mitomycin-C and vinblastine as necessary. At the time of diagnosis, 17 patients who had no evidence of distant metastasis, i.e., stage III B disease, had disease-free survival ranging from 5 to more than 84 months, with a median of 30 months, and an overall survival of 7 to more than 120 months with a median of 32 months. The 5-year survival rate was 18%. The other 11 patients who had distant metastases, i.e., stage IV disease, had an overall survival ranging from 4 to 14 months. The results of this approach of initial systemic chemotherapy followed by local-regional cytoreductive therapy, then systemic therapy, might suggest some survival benefits in patients with stage III disease.

The genetically determined ability to metabolize the antihypertensive drug debrisoquine has been proposed as a genetic risk factor for primary carcinomas of the lung. To test this hypothesis, the metabolism of the drug was evaluated in a case control study. The subjects were characterized by their ability to metabolize debrisoquine after receiving a test dose of the drug followed by the collection of an 8-hour urine sample. They were classified by laboratory analysis into one of the following three groups: extensive, intermediate, and poor metabolizers. Poor metabolizers comprise 10% of the population and are unable to hydroxylate the drug. This group was expected to be at highest risk for deleterious effects from this medication. A protocol was created that included patient education and blood pressure monitoring to administer this medication safely to a group of patients with cancer who were already compromised. Although poor metabolizers showed a small decrease in systolic and diastolic blood pressure, no significant hypotensive episodes or clinical sequelae were observed in any of the groups. These data suggest that debrisoquine can be administered safely in a controlled clinical setting and will be useful for the characterization of lung cancer patients in biochemical epidemiology studies.

347 Background: 9,704 was the first phase 3 pancreatic cancer trial to validate the prognostic value of postresection CA19-9 for overall survival (OS), with values > 90/180 associated with worse OS. All pts received adjuvant gemcitabine or 5-FU and chemo-radiotherapy (RT). This analysis evaluates patterns of disease failure. Methods: SMS was negative, positive, or unknown. CA19-9 was analyzed at cut points 90, 180 and continuously. LRF and DF were estimated by cumulative incidence and Gray’s test compared. Cox hazard models were used for multivariate analyses (MVA) and included treatment, tumor site, size and nodal status. To adjust for multiple comparisons a p-value < 0.01 is statistically significant and 0.01 to < 0.05 a trend. Results: 538 pts accrued, with 451 eligible and analyzable for SMS and 385 for CA19-9. For CA19-9, 132 (34%) were Lewis Antigen negative (no CA19-9 expression), 200 (52%) < 90 and 220 (57%) < 180. 188 (42%) had negative margins, 152 (34%) positive and 111 (25%) unknown (i.e., no margin comment in path report; shown to have outcomes similar to negative margin pts). Pts with CA19-9 ≥ 180 were more likely to have tumors ≥ 3 cm and pts with positive SMS more likely to have KPS 60 - 80, T3/T4, or N1 disease. On univariate analysis (UVA) CA19-9 cut at 90 was associated with significant increases in both LRF (trend) and DF; in the gemcitabine arm this was seen in DF, not in LRF; in the 5-FU arm it was seen in both. Results were similar at the 180 cut point and continuously. SMS on UVA was not associated with increase in LRF/DF; see Table. On MVA, CA19-9 > 90 was significantly associated with LRF and DF; positive SMS showed only a trend for DF. Conclusions: Postresection CA19-9 has significant association with both LRF and DF not seen with SMS. These findings support continued use of RT in trials and consideration of dose intensification among pts with elevated postresection CA19-9. Grants: NCI U10, CA21661, CA37422, CA180868, CA180822. Clinical trial information: 0000000. [Table: see text]

Hepatic resection results in significant morbidity and mortality primarily related to intraoperative blood loss. Intermittent vascular inflow occlusion (VO) and low central venous pressure (CVP) during hepatectomy have been used to reduce blood loss. To determine the benefit of VO and low CVP, we reviewed the outcomes of 168 consecutive patients who underwent liver resection. The results of 78 patients who had undergone hepatic resection between 1993 and 1998 with the use of VO and low CVP (post-VO/CVP) were compared to the previous 90 patients who had undergone hepatectomy without VO and low CVP (pre-VO/CVP) between 1979 and 1992. Hepatectomies were performed for metastatic disease (65%), hepatoma (20%), and benign tumors (15%). Resections included 18 trisegmentectomies, 67 lobectomies, and 83 segmental resections. Patients in both groups were similar with regard to extent of resection. Post-VO/CVP patients had significantly lower median estimated blood loss (725 ml vs. 2300 ml, P0.001), less postoperative morbidity (10.3% vs. 22. 2%, P = 0.038), lower in-hospital mortality (2.6% vs. 10%, P = 0. 050), fewer days in the intensive care unit (1.6 +/- 0.1 days vs. 5. 6 +/- 1.2 days, P = 0.003), and shorter overall length of stay (8.0 +/- 0.5 days vs. 15.0 +/- 1.6 days, P0.001) than pre-VO/CVP patients. These data suggest that VO and low CVP during liver resection may improve patient outcomes.

A variety of malignancies, including hematologic malignancies, Kaposi's sarcoma, as well as adenocarcinomas and squamous cell carcinoma have been reported in association with acquired immune deficiency syndrome. Tumors of the umbilical area are unusual and can represent lesions of urachal origin. These may require extensive resection and are associated with a poor prognosis. We describe here a case of a young woman with AIDS who developed a squamous cell carcinoma of the umbilicus which suggests more than a casual relationship between these two conditions.

Posterior layer closure of deeply located anastomoses including those performed in the course of low anterior rectal resection, total gastrectomy, and esophagogastrectomy, are often difficult. Usually five to six seromuscular or through-and-through posterior wall sutures are inserted sequentially and the loop or cut end of bowel is advanced over these parallel sutures. The sutures are then tied down. Entanglement of these sutures in a deep surgical field with limited access can lead to tears in the bowel wall. In addition, uneven and nonsequential tying of these sutures may compromise the anastomosis itself. We have described here how manual anastomosis in deep, hard to reach surgical fields can be better accomplished with the use of an instrument-holding clip. Use of the described instrument-holding clip, to clearly delineate and anchor each suture in sequence, eliminates these problems. An easily available device, it can save operative time, facilitate a more even anastomosis, and decrease the chance of bowel wall tearing, thus enhancing the security of the anastomosis.

When chest roentgenograms fail to reveal the presence of a lesion in a patient suspected t o have bronchogenic carcinoma, perfusion lung scanning with radioiodinated macroaggregated human albumin (1-131 M.A.A.) is of great help in the diagnosis and localization of the bronchogenic carcinoma. Marked decrease in perfusion of the affected lung area is detected on lung scan in early hilar and parahilar lesions which are not even seen on chest roentgenograms. Two such cases are presented. Lung scan is safe and easy to perform.

The authors have used imidazole carboxamide (DTIC) in vascular isolation and hyperthermic perfusion for melanoma. The regional and systemic toxicity and complications of this procedure were studied in 40 cases with Stage III (15) and Stage I (25) melanoma. Technetium 99m-labelled serum albumin crossover and pharmacokinetic studies were done simultaneously to see if these correlate with toxicity. Local toxicity on muscles, nerves, skin, and arteries was conspicuously absent despite using dosages of 2 g/m2 (40-45 mg/kg) for the lower extremity and 1.2 g/m2 (24-28 mg/kg) for the upper extremity. Skin and core temperature were raised to 39 degrees C to 40 degrees C. Deep vein thrombosis was noted in three patients. No death or gangrene of the extremities occurred. Local infection was noted in only one patient. Fourteen patients (35%) manifested bone marrow toxicity (leukocyte count of 4000/mm3 or platelets of 100,000/mm3) in the second or third week after perfusion. Severe hematologic toxicity was seen in two instances. Dosages of DTIC greater than 40 mg/kg were associated with toxicity in 65% of the patients. No bleeding complications occurred in seven patients with thrombocytopenia. Measurement of crossover and recovery of radionuclide were not reliable indicators of subsequent systemic toxicity. Perfusion fluid balance data also were of no predictive value. Forty-seven percent of the administered DTIC was recovered in washout fluid. Of this, less than 2% was converted to its metabolites, that is aminoimidazole carboxamide and 2-azahypoxanthine. Thirty-five of 40 patients experienced mild nausea and vomiting. Transient and mild hepatotoxicity was noted in seven patients. It appears that DTIC hyperthermic isolation perfusion is a safe procedure, however, the total dosage should be below 40 mg/kg to avoid hematologic toxicity.

Continuous infusion chemotherapy via hepatic artery using newly available mechanical devices is frequently used to treat hepatic metastases to achieve a high concentration of 5-fluorouracil (5-FUra) in the hepatic circulation while minimizing systemic exposure. We compared four routes of intrahepatic administration to find out the best one in the canine model. To ascertain this data, 5-FUra (30 mg/kg) was given as a continuous infusion over a 3 hr period into either a systemic vein (femoral), portal vein, hepatic artery, or hepatic artery distal to its ligation after hepatic dearterialization. A total of eight dogs were studied. During 5-FUra infusion, concomitant blood samples were taken from the inferior vena cava and hepatic vein at 1, 2, 3, 5, 10, 15, 30, 60, 120, and 180 min. 5-FUra levels were determined in plasma by high-performance liquid chromatography. Blood flow in the portal vein and hepatic artery was measured by an electromagnetic flowmeter. The data described by a multicompartmental model, including the measured flows, had separate hepatic arterial and portal compartments with elimination from each described by linear kinetics. Mean area under the curve values in microgram/ml X min and the ratios of the systemic/hepatic vein areas following 5-FUra infusion via systemic, portal vein, hepatic artery, or hepatic artery after dearterialization routes were: 975/539 (R = 1.80), 939/748 (R = 1.35), 211/454 (R = 0.46), and 562/1,424 (R = 0.39). The results indicated that the administration of 5-FUra via the hepatic arterial route distal to its ligation results in the highest hepatic vein drug levels with the smallest systemic/hepatic vein exposure ratio, followed by intra-arterial route, while systemic and portal vein routes were not nearly as advantageous as the intra-arterial routes.

To study the biologic behavior and natural history of this rare but challenging tumor faced by oncologists, a clinicopathologic study of 42 patients with histologically proven adrenal cortical carcinoma from Roswell Park Memorial Institute (1929--1977) was done. These constituted .04% of all cancer cases and 0.2% of all autopsy cases. Age range was 3--74 years with median of 53 years; female to male ratio was 1.5 to 1. Clinical manifestations were: abdominal mass (36%), metastatic disease (30%), hormonal excess (17%) and weakness with lethargy (17%). Nine of ten functioning tumors were seen in female patients. Tumors arose in left adrenal in 26 patients, right adrenal in 12, and in four the site could not be determined because of bilateral presence of cancer. Median duration of symptoms was six months. At diagnosis, 52% had distant metastases, 41% had locally advanced tumor and 7% had tumor confined to adrenal. Sixteen patients underwent "curative" resection. Tumor diameter ranged from 1--30 cm with median of 10 cm. Of 28 patients who received different chemotherapeutic regimens, three (11%) had objective response; four of ten patients had objective response to radiation therapy. Overall median and five-year survival rates were 14 months and 24%. Prolonged survival (P less than .05) was noted in women, patients who had "curative" resection, a disease-free interval of more than 12 months, and tumor size greater than 10 cm diameter. Patients with functional tumors had longer median survival than those with non-functional ones (28 vs. 12), but P value was greater than .05. A second primary cancer was noted in 22.4% of cases, breast and lymphoma being the most common. At autopsy in 31 patients, the most common metastatic sites were retroperitoneal lymph nodes 68%, lung 71%, liver 42%, and bone 26%. To improve survival, an aggressive surgical approach is recommended to extirpate the tumor with involved organs and retroperitoneal lymph nodes. Adrenal carcinoma should be suspected in patients with metastatic cancer with an occult primary.

Thirty-two patients with histologically proved metastatic malignant melanoma of the brain were evaluated. Intracranial surgery was performed in 19 and was considered not indicated in 13 patients. Following intracranial surgery, satisfactory improvement in neurologic deficits was observed in 14 (74%) patients. The median survival after occurrence of brain metastases was 5–6 months (1 – 15 months) for the surgical group; and for the nonsurgical group, patients with multiple brain metastases and multiple visceral involvement did not survive beyond a median of 1 month (range 0.5–6 months). Intratumor hemorrhage with substantial intracerebral hematoma was present in 7 (41%) out of 17 craniotomies. The overall incidence of intratumor hemorrhage found at autopsy was 59% for the entire series. Among ail the cases with intratumor hemorrhage, only 2 patients who received chemotherapy after craniotomy developed thrombocytopenia with fatal intracranial hemorrhage. The latter cause-and-effect correlation could not be assessed in the other patients. As a result of this retrospective study, we have observed that patients with malignant melanoma and evidence of single brain metastasis without multiple visceral involvement seemed to benefit more from palliative surgery. Moreover, intratumor hemorrhage was a frequent occurrence and should be considered in the differential diagnosis of a patient with malignant melanoma and rapid deterioration of neurologic deficits.

Eighty-eight cancer patients with the presence of one or more adverse factors for healing (carcinomatosis, adhesions, prior chemotherapy and radiation therapy, bowel obstruction, anemia, and low leukocyte count or albumin value) were prospectively randomized to undergo conventional two-layer hand suturing (45 patients) or mechanical stapling with a GIA/TA instrument (U. S. Surgical Corp., Norwalk, CT) (43 patients) of the large or small bowel anastomosis. Age, sex, complete blood count findings, and all biochemical plasma values were comparable in both groups. The anastomosis took an average of 19 minutes for the sutured and 9 minutes for the stapled technique (P = 0.0001), but the average length of operation, postoperative return of bowel function, and hospital stay were comparable in both groups. Bowel fistula was seen in one case of stapled anastomosis (P = not significant). The pulmonary and wound complication rates were the same in both groups. Of the four deaths (4.5%) due to causes unrelated to bowel anastomosis, three occurred in the stapled and one in the sutured group. It was concluded that a stapled anastomosis is as safe as a sutured one in patients with advanced-stage cancer. It saves time in anastomosis, but does not save time in postoperative return of the bowel function and hospital stay.

Ocular melanoma is the most common malignant tumor of the eye and accounts for 70 to 80 percent of all extracutaneous melanomas. Its biologic behavior differs from that of its cutaneous counterpart. To elucidate this, 62 patients with histologically proven melanoma of eye (58 uveal tract and 4 conjuntiva) at Roswell Park Memorial Institute from 1945 to 1977 were studied. The prominent contradistinctions from other head and neck melanomas were (1) a very high percentage of patients had either locally advanced or systemic disease at diagnosis, although the eye is the most sensitive organ; (2) regional lymph node involvement was absent even in the late stages of disease; (3) hematogenous spread involved single organs, most commonly the liver and the lung; (4) local recurrence was rare; (5) most recurrences occurred evenly in first 10 years after treatment; (6) regional resection, chemotherapy or both are advocated for distant metastases since they are confined to a single organ and are amenable to it; and (7) despite hematogenous spread and advanced disease at diagnosis, the overall prognosis of ocular melanoma is comparable to that of cutaneous melanoma.

One hundred fifty-two patients with squamous cell carcinoma of the larynx were studied. The disease free survival and overall survival rates were correlated to 12 variables. Seven of them seemed to affect survival. Poor prognosis was related to (1) advanced stage of disease at diagnosis, (2) cord fixation and massive local invasion, (3) ulceration of the primary tumor, (4) lymph node metastases at diagnosis, (5) glottic lesions had a poorer prognosis than supraglottic ones, (6) locoregional recurrences, and (7) male gender. However, most of these significant differences were in disease-free survival, and only primary tumor staging; lymph node status; and locoregional recurrences affected overall survival. On the other hand, the other five variables showed no effect on either disease-free or overall survival rates. These included age, race, cell differentiation, type of recurrence, and the initial definitive therapeutic modality.

Preoperative pulmonary function test results in 258 patients who underwent pulmonary resection for bronchogenic carcinoma were studied in relation to postoperative mortality from cardiopulmonary complications. Poor outcome of surgery was related to the maximal breathing capacity value below 59 per cent of the predicted normal, age over sixty-nine years, and abnormal electrocardiographic findings. Combinations of these factors were associated with a very high mortality (56 per cent). This group of patients needs further evaluation on an individual basis to identify the risk of pulmonary resection. A formula to predict the risk of surgery based on the maximal breathing capacity value is suggested. Values for one second forced expiratory volume and vital capacity were of no use in predicting the outcome of surgery.

The effect of known chemotherapeutic programs in patients with breast cancer who developed metastasis during or after adjuvant chemotherapy with L-PAM plus 5-FU (PF) were studied. Thirteen patients failed while receiving adjuvant therapy at 3-22 months from the time therapy started. Three patients failed 6-28 months after 2 years of therapy. Thirteen patients received PF followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) at the time of progression on PF. Of these, ten received Adriamycin and vincristine (AV) at the time of progression on CMF. The response to CMF was 7%. No patient responded to AV after progression on CMF. Two of three patients treated with AV after failure on PF did respond, but both for only 6 months. This suggests that adjuvant therapy may render the tumor less responsive to further chemotherapy. Since most patients failed while on adjuvant therapy, this may indicate a poor prognosis regardless of the agents used.

Fifteen malignant melanomas were subjected to chromosomal analysis, in order to determine whether the number of chromosomes in a tumor cell could be correlated to a clinical prognosis. The protocol involved a direct technique which utilized a Colcemid blockade of spindle formation in mitosis to allow study of metaphase chromosomes. The direct method was chosen to reveal chromosome changes in the tumor cell in situ rather than changes in the cultured cell. Two tumors yielded chromosome spreads which could be counted and correlated with a clinical prognosis. Failure to obtain other adequate chromosome spreads were accounted for by the presence of tissue necrosis and the absence of viable tumor cells.

Fifty-one patients (32 previously untreated, 19 previously treated) with advanced squamous cell carcinoma of the head and neck received a single course of combination chemotherapy consisting of high dose cis-platinum (DDP), bleomycin (Bleo), +/- high dose methotrexate (MTX). Thirty-three (65%) patients responded to therapy; 5 (10%) of these patients had a complete response. Previously untreated patients and those who received the three drugs (DDP, Bleo and MTX) had the highest response rates. The duration of response was 8 to 12 weeks. Seven (15%) patients showed a two-year survival rate. All nonresponders were dead of disease within two years. Three (56%) of the five complete-response patients and 4 (21%) of the partial-response patients survived for two years. The role of preoperative chemotherapy in head and neck cancer is yet to be conclusively defined.

Forty-one 67Ga images were obtained for 33 patients with a diagnosis of soft-tissue sarcoma or chondrosarcoma. Tumor was detected in 27 cases of soft-tissue sarcoma; 25 (93%) of these were found on the Ga scans. The overall accuracy of scanning was 95.1%. All patients with positive scans had tumor present. In soft-tissue sarcoma patients the scan detected the tumor in 39 out of 45 sites. Ga scintigraphy was found to be useful in the initial evaluation and follow-up of these patients. If the Ga citrate scan is positive at multiple sites, the possibility of tumor being present is 100% with a false negative rate of 16%.

To evaluate an effective, cell-cycle-specific combination chemotherapy which could be administered on an outpatient basis, COMB of Maryland (Cytoxan, Oncovin, methotrexate and bleomycin) was used in 20 patients with stage IV squamous cell carcinoma of head and neck origin. All patients had unresectable but measurable disease. Nine patients had distant metastases. Prior to this chemotherapy, 15 (75%) patients underwent radiation therapy, 12 (60%) had radical surgery, and 3 (15%) were administered other chemotherapeutic drugs. The distribution of the primary site of tumor was identical to the overall distribution of squamous cell carcinoma of head and neck found in this country. Drug dosages were: Cytoxan 100 mg/m2 p.o. days 1-14, Oncovin 1 mg/m2 IV days 1 and 8, methotrexate 25 mg/m2 IV days 1 and 8, and bleomycin 15 units/m2 IM days 1 and 8. This cycle was repeated every four weeks. Two (10%) patients had complete response and 7 (35%) had partial response, thus giving the total response rate of 9 (45%). Seven (35%) patients had static disease and 4 (20%) had progression of disease. Duration of response was from 8 to 26+ weeks with a median duration of 17+ weeks. Response rate was statistically related to performance status and previous chemotherapy. However, it was not related to age, sex, site of origin, previous radiation therapy, or differentiation of the tumor. Increased survival (P < 0.01) was seen in responders (median 16+ weeks) as compared to nonresponders (9 weeks). Hematologic toxicity was seen in 9 (45%) patients, resulting in one chemotherapy-related death. Overall, this chemotherapy has been well tolerated on an outpatient basis. Although 15 (75%) patients received prior radiation therapy, the results were comparable to those obtained by other, more toxic combination chemotherapeutic regimens.

Hepatic dearterialization by ligation of the main hepatic artery followed by local intraarterial chemotherapy was performed in 24 patients with clinically isolated but unresectable hepatic metastasis after local resection of carcinoma of the colon. Computed tomography of the abdomen and laboratory parameters were used both to stage and follow-up these patients. Computed tomography changes following dearterialization and chemotherapy of the liver are described. Computed tomography is a valuable technique for both staging and follow-up this group of patients.

Adequate flow cytometric DNA analysis comparing primary and concurrent metastatic squamous cell carcinoma of the head and neck has not been done in the past. The purpose of this study was to define any differences between the primary and concurrent metastasis of each patient with respect to flow cytometric parameters and histologic grade. Paraffin-embedded archival specimens from 28 patients with primary and metastatic tumors were prepared into nuclei and analyzed by flow cytometry using human lymphocyte standards. The mean DNA index was 0.82 for primary tumors and 0.83 for the metastases. Aneuploidy was found in 68 percent of primary tumors and in 82 percent of metastases. The percentage of cells in the proliferative fraction was 40.4 in the primary tumors and 24.5 in the metastases. A direct correlation was found between the differentiation of the primary and metastatic tumors. No survival difference was discovered among the flow cytometric parameters and histologic grade. We conclude that there is no difference between the primary and concurrent metastasis in squamous cell carcinoma of the head and neck with regard to DNA index, aneuploidy, or histologic grade.

• Fifty-one patients with stage III or IV squamous cell carcinoma of the head and neck who received induction chemotherapy with cisplatin and bleomycin sulfate with and without high-dose methotrexate were studied. The relationship of the prechemotherapy levels of serum alkaline phosphatase, lactic dehydrogenase, SGOT, SGPT, BUN, creatinine, calcium, total protein, albumin, hemoglobin, uric acid, and bilirubin and the WBC and platelet counts was correlated with the response rate. The overall response rate was 65%. No notable relationship between any of the laboratory values and the response rate was found. In contrast to an earlier report, patients with a low alkaline phosphatase level responded as well as patients with an elevated serum alkaline phosphatase level. (Arch Otolaryngol1982;108:28-29)

MALIGNANT melanoma has no predictable clinical behavior. The Breslow depth and Clark's level of invasion are important prognostic factors, but their prognostic values are overshadowed by the presence of regional lymph node metastasis (stage III disease). 1 In patients with stage III disease, the number and size of lymph nodes involved are prognostic indicators. For patients at high risk of recurrence, various therapeutic trials have tested surgery and radiation therapy, surgery and regional perfusion therapy, and immunotherapy and various chemotherapeutic agents, alone and in combinations. These studies have helped to define prognostic factors, but have had little impact on disease-free or overall survival. Response rates for treatment of advanced disease have varied considerably and may be related to sites and bulk of disease. Assessment of the amount and the extent of disease is necessary for evaluation of any therapy. Computed tomography (CT) has proved accurate in evaluating adenopathy, 2-4 but