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Background: Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, demonstrated an overall response rate of 63.0% in 165 heavily pretreated patients with relapsed or refractory multiple myeloma in the phase 1/2 MajesTEC-1 study. Cytokine release syndrome (CRS), a known manifestation of T-cell redirection, was observed in 119 of 165 patients (72.1%). Methods: Patients received once-weekly teclistamab 1.5 mg/kg subcutaneously after two step-up doses (0.06 and 0.3 mg/kg). CRS was graded according to American Society for Transplantation and Cellular Therapy criteria and managed according to the study protocol, including use of tocilizumab and/or steroids. Results: Most cases of CRS occurred during the step-up dosing schedule of teclistamab and were grade 1 (50.3% of patients) or grade 2 (21.2% of patients); a single case of grade 3 CRS was reported in a patient with concurrent grade 3 pneumonia. All CRS cases resolved and none led to treatment discontinuation. Overall, 33.3% of patients had >1 CRS event; CRS recurrence was reduced when tocilizumab was administered for the first CRS event compared with when it was not (20.0% vs. 62.2%, respectively). Baseline characteristics such as tumor burden and cytokine levels did not appear to predict CRS incidence or severity. Conclusions: Findings of this study support the need for preemptive planning and prompt management of CRS in patients treated with T-cell–engaging bispecific antibodies. Intervention with tocilizumab for CRS appears to decrease the likelihood of patients experiencing subsequent CRS events without compromising response to teclistamab. Plain language summary: Cytokine release syndrome (CRS), observed in 72.1% of patients treated with teclistamab in the MajesTEC-1 study, was mostly grade 1 or 2 and manageable, without requiring treatment discontinuation. Most CRS occurred during the step-up schedule, requiring vigilance during treatment initiation. Ensure fever is resolved and patients have no signs of infection before initiating the teclistamab step-up schedule or administering the next teclistamab dose, to avoid exacerbating CRS. Tocilizumab reduced the risk of subsequent CRS in patients receiving it for their first CRS event (20.0% vs. 62.2% in those not receiving it), without affecting response to teclistamab. No baseline characteristics, including tumor burden or cytokine levels, appeared to clearly predict for CRS occurrence or severity.

Background Although lymphovascular invasion (LVI) has been associated with a poor outcome in patients with breast cancer, it is not included in most internationally recognized staging systems, including the American Joint Committee on Cancer tumor, lymph node, metastasis (TNM) classification. This is mainly because it remains unclear whether the presence of LVI is an independent, high-risk criterion in clinically relevant staging subgroups. Methods The current study was based on a large and well characterized consecutive series of patients who had operable (pathologic T1 [pT1]-pT2, pathologic N0 [pN0]-pN3, M0) breast cancer (3812 informative cases) who were treated according to standard protocols at a single institution and who had long-term follow-up to assess the prognostic value of definite LVI in clinically and molecularly relevant staging subgroups. Results LVI was strongly associated with both breast cancer-specific survival (BCSS) and distant metastasis-free survival (DMFS) in the entire series and in different subgroups. Multivariate analyses identified LVI as an independent predictor of both BCSS and DMFS in patients with operable breast cancer overall; in the TNM clinical subgroups pT1a-pT1c/pN0 and pT2/pN0; and in the molecular classes estrogen receptor (ER)-positive, ER-negative, human epidermal growth factor 2 [HER2]-negative, and triple-negative. In patients who had lymph node-negative tumors, LVI could be used as a high-risk criterion providing survival disadvantage equivalent to that provided by 1 or 2 involved lymph nodes (pN0 to pN1) and to that provided by 1 size category (pT1 to pT2). The use of immunohistochemistry for detecting an endothelial-specific marker contributed to the prognostic significance of LVI when applied to routine LVI negative/possible cases. Conclusions LVI provided a strong predictor of outcome in patients with invasive breast cancer and should be incorporated into breast cancer staging systems.

BACKGROUND: The authors studied the survival and long-term morbidities of children with nasopharyngeal carcinoma (NPC). METHODS: This was a retrospective review of children with NPC who were treated at St. Jude Children's Research Hospital between 1961 and 2004. Prognostic factors and long term effects of therapy were analyzed. RESULTS: Fifty-nine patients (median age, 14.1 years) were identified. Most were male (66.1%) and black (54.2%) and had lymphoepithelioma (93.2%). Thirty-five patients had stage IV disease (59.3%), 20 patients had stage III disease (33.9%), and 4 patients had stage II disease (6.8%). All patients received radiotherapy (RT) to the primary tumor, and most received cervical RT (98.3%) and chemotherapy (88.1%). The 15-year survival and event-free survival (EFS) rates were 67.2% ± 7.5% and 63.5% ± 7.8%, respectively. Five patients (8.5%) developed subsequent malignancies 8.6 to 27 years after NPC diagnosis. EFS was improved in patients who were diagnosed after 1980 (74.8% ± 10% vs 45.5% ± 10.1%; P = .031), in patients who had stage III disease compared with patients who had stage IV disease (79.3% ± 9.6% vs 56.2% ± 11.8%; P = .049), in patients who received cisplatin (81% ± 10.7% vs 45.8% ± 9.7%; P = .013), and in patients who received ≥50 grays of RT (71.4% ± 9.3% vs 43.8% ± 11.6%; P = .048). White patients had higher distant failure rates than black patients (41.7% ± 10.4% vs 15.6 ± 6.5%; P = .045). The 15-year cumulative incidence (CI) of any morbidity was 83.7% ± 5.4%, the CI of sensorineural hearing loss was 52.9% ± 6.7%, the CI of primary hypothyroidism was 42.7% ± 6.6%, and the CI of growth hormone deficiency (GHD) was 14.1% ± 4.7%. Dose-response relations were observed between the RT dose and primary hypothyroidism and GHD. CONCLUSIONS: The outcome of children with NPC improved over the past 4 decades with the use of cisplatin-based chemotherapy and higher RT doses. However, many survivors had long-term treatment-related morbidities. Cancer 2011. © 2010 American Cancer Society.

Reports have demonstrated the superior activity of combining both irinotecan and oxaliplatin (FOLFOXIRI) therapy. An option for gaining similar benefits with less toxicity would be the administration of irinotecan through a hepatic artery approach. The aim of this study was to assess the response and adverse event rates for irinotecan drug-eluting beads (DEBIRI) with folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) and bevacizumab as a first-line treatment for unresectable colorectal liver metastasis.Patients with colorectal liver metastases were randomly assigned to modified FOLFOX (mFOLFOX) and bevacizumab or mFOLFOX6, bevacizumab, and DEBIRI (FOLFOX-DEBIRI). The primary endpoint was the response rate. The secondary endpoints were adverse events, the rate of conversion to resection, and progression-free survival.The intention-to-treat population comprised 70 patients: 10 patients in the pilot and then 30 patients randomly assigned to the FOLFOX-DEBIRI arm and 30 patients randomly assigned to the FOLFOX/bevacizumab arm. The 2 groups were similar with respect to the extent of liver involvement (30% vs 30%), but a greater percentage of patients in the FOLFOX-DEBIRI arm had an Eastern Cooperative Oncology Group performance status of 1 or 2 (57% vs 31%) and extrahepatic disease (56% vs 32%, P = .02). The median numbers of chemotherapy cycles were similar (10 vs 9), and there were similar rates of grade 3/4 adverse events (54% for the FOLFOX-DEBIRI group vs 46% for the FOLFOX/bevacizumab group). The overall response rate was significantly greater in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm at 2 (78% vs 54%, P = .02), 4 (95% vs 70%, P = .03), and 6 months (76% vs 60%, P = .05). There was significantly more downsizing to resection in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm (35% vs 16%, P = .05), and there was improved median progression-free survival (15.3 vs 7.6 months).The simultaneous administration of mFOLFOX6 (with or without bevacizumab) and DEBIRI through the hepatic artery (FOLFOX-DEBIRI) is safe and does not cause treatment delays or increase the systemic toxicity of chemotherapy. This strategy leads to improved overall response rates, improved hepatic progression-free survival, and more durable overall progression-free survival in patients downsized to resection.

BACKGROUND Patients with metastatic colorectal carcinoma (MCC) to the liver receive conflicting management recommendations because of the lack of prospective randomized controlled trials (RCTs) clarifying the optimal management in this disease. The oabjective of the current study was to evaluate the reporting of prognostic factors in MCC from chemotherapy and surgery trials and evaluate the ability to compare these results across treatments. METHODS RCTs and retrospective series of greater than 75 MCC patients published between 1980–2004 were reviewed to identify 10 critical prognostic elements of overall survival reported in both types of journals. RESULTS A review 92 RCTs and 116 retrospective reports with 64,898 patients analyzed found 7 (3%) reporting all prognostic factors, with both studies demonstrating no difference in the success of reporting criteria met. The only criterion that was universally reported among both chemotherapy and surgery trials was the mortality rates of the study. All remaining prognostic factors in the evaluation of overall survival were significantly different between both chemotherapy and surgical studies. Considerable variation was observed in the disease-free interval, number of hepatic metastases, size of hepatic metastases, and performance status, and were significantly different among some of the most significant factors for patients evaluating treatment: complication reporting, surgical margin evaluation, and overall response rate. CONCLUSIONS The reporting of results in MCC in chemotherapy trials and surgical reports is limited to general outcomes, with a paucity of prognostic factors, which hinders any ability to compare results across treatments. A mandatory reporting criteria of all metastatic colorectal trials is imperative to optimally manage these patients in both academic and community centers. Cancer 2006. © 2006 American Cancer Society.

BACKGROUND Chemotherapy-induced nausea and emesis (CINE) is one of the most dreaded side effects of cancer therapy. To investigate the influence of these symptoms on a patient's quality of life (QOL), a validated tool measuring many domains is needed. METHODS A QOL questionnaire consisting of scales from the European Organization for Research and Treatment of Cancer QLQ-C30, the Morrow Assessment of Nausea and Emesis, the Osoba Nausea and Emesis Module, and new items specific to nausea, emesis, and retching was constructed and administered daily for 7–9 days to outpatients receiving emetogenic chemotherapy. RESULTS Test-retest and internal consistency reliabilities ranged from 0.44 to 0.84 and from 0.59 to 0.85, respectively. Item and scale correlations indicated good convergent and discriminant validity. Scales and items measuring similar factors (e.g., severity of emesis and severity of nausea) had strong correlations than did scales measuring dissimilar factors (e.g., cognitive functioning and physical functioning). The validity of known groups was demonstrated by significant differences (P < 0.01) in patients' QOL scores between days with no episodes of nausea, emesis, or retching, days with 1 or 2 episodes, and days with more than 3 episodes. Patients' QOL significantly decreased as the number of episodes per day increased (P < 0.001). CONCLUSIONS A CINE QOL questionnaire that successfully measures the short-term impact of nausea, emesis, and retching on patients receiving emetogenic chemotherapy has been developed, largely as a battery of preexisting questionnaires. The psychometric properties of the new questionnaire show adequate reliability and validity to warrant its use in clinical trials and outcomes studies. CINE adversely affects many domains within a patient's QOL. Cancer 2003;98:645–55. © 2003 American Cancer Society. DOI 10.1002/cncr.11540

BACKGROUND There has been an increasing incidence and mortality from peripheral cholangiocarcinoma (PC) in the United States over the past 24 years. PC has been classified into two principal types, a mass-forming type and a periductal-infiltrating type, with a significant difference in the clinical behavior between the two. A third type, demonstrating a noninvasive intraductal growth of PC, was described as papillary PC. Rarely, papillary hepatic tumors composed of oncocytic cells have been described. Intraductal oncocytic papillary carcinomas (IOPCs) of the liver present as large, mucin-filled, cystic lesions lined by noninvasive or focally microinvasive oncocytic tumors. METHODS From June 1999 to August 2001, three patients with hepatic IOPCs were identified in the files of the Hepatobiliary Service, Department of Surgery, and the Department of Pathology at Memorial Sloan-Kettering Cancer Center. They form the basis of this study. We report the clinicopathologic presentation, as well as the outcome, with a review of the literature. RESULTS All three cases presented with well defined intrahepatic cystic masses ranging in size from 7.2 to 21.1 cm. The most prominent cells of the lining epithelium were columnar with oncocytic features showing abundant eosinophilic granular cytoplasm and centrally located nucleoli. All three patients underwent resection with one demonstrating local bile duct recurrence that was managed with stenting. Review of the literature has identified 39 patients with papillary PC and 2 patients with IOPC. The biology of these reported cases has been variable with overall survival better than that of nonpapillary PC patients, with recurrence in 15% of the reported cases. CONCLUSION Papillary PC is a rare type of cholangiocarcinoma that includes an interesting variant: IOPC. These tumors are predominantly found in men, who present with large (> 5 cm) mucinous cystic lesions of the bile duct. A noninvasive histology is seen, and long-term survival may be achieved with complete resection. Invasive variants of IOPC have been reported in the literature and have a worse overall prognosis. Cancer 2002;95:2180–7. © 2002 American Cancer Society. DOI 10.1002/cncr.10934

BACKGROUND Despite advances in cardiopulmonary resuscitation and the education of its providers, survival remains dismal for cancer patients suffering in-hospital cardiac arrest. In an effort to determine if characteristics of cardiac arrest would represent a useful parameter for prognostication and recommendations regarding the suitability of ongoing resuscitation for various groups, this review was undertaken for patients who experienced in-hospital cardiac arrest. METHODS A retrospective study of data gathered between January 1993 and December 1997 was undertaken in a 518-bed comprehensive cancer center. The records of 243 inpatients who experienced cardiac arrest and received cardiopulmonary resuscitation were reviewed, and their course observed until hospital discharge or death. RESULTS Sixteen of 73 patients (22%) who had sudden, unanticipated cardiac arrests survived to be discharged from the hospital; however, none (0 of 171) of the patients who experienced an anticipated cardiac arrest survived (P < 0.001). Logistic regression analysis revealed that anticipated cardiac arrest associated with metabolic derangement was an independent predictor of hospital mortality. CONCLUSIONS Patients experiencing an anticipated cardiac arrest, the course of which could not be interrupted through aggressive management in an intensive care unit, have an extremely poor prognosis. Ongoing resuscitative measures in these patients need not be routinely provided. The authors suggest an algorithm for resuscitation that evaluates the characteristics of the arrest as a prognostic factor. This algorithm should be implemented once progressive deterioration spirals toward cardiac arrest that cannot be prevented. Such an approach should avoid painful and costly interventions that are futile with the present techniques of cardiopulmonary resuscitation. Cancer 2001;92:1905–12. © 2001 American Cancer Society.

BACKGROUND Discrepancies between the severity of toxicities reported in early clinical trials and recent clinical experience with vancomycin have led to confusion regarding the need for routine serum vancomycin level monitoring and discontinuation of vancomycin when toxicities occur. Therefore, the authors examined the incidence, outcomes, and predictive factors of vancomycin-associated toxicities in general oncology practice with the goal of developing clinically relevant prediction rules and guidelines. METHODS All 742 consecutive cancer patients who received vancomycin at a comprehensive cancer center during a 3-month period were followed prospectively for the development and outcome of phlebitis, rash, ototoxicity, and nephrotoxicity. Logistic regression was used to derive a multiple variable model of the risk of nephrotoxicity. A clinical prediction rule, the Nephrotoxicity Risk Score, was developed from the risk model and validated prospectively. RESULTS Phlebitis occurred in 3% of patients (95% confidence interval [95% CI], 2-4%), predominantly those with recently inserted central venous catheters. Rashes occurred in 11% of patients (95% CI, 9-13%); however, all but 4 patients also were receiving β-lactam antibiotics. Clinical evidence of ototoxicity developed in 6% of patients (95% CI, 4-9%) who were receiving vancomycin plus other ototoxic agents and only 3% of patients (95% CI, 2-5%) not receiving other ototoxic agents (P = 0.08). Nephrotoxicity occurred in 17% of patients (95% CI, 15-20%). Logistic regression revealed that factors associated with an increased risk of nephrotoxicity included administration of other mild to moderate (P = 0.01) or severely nephrotoxic agents (P 40 (P = 0.002). Elevated serum vancomycin peak levels did not reliably predict subsequent nephrotoxicity. CONCLUSIONS Vancomycin-associated toxicities usually are mild and self-limiting. Some patients are at a significantly higher risk of nephrotoxicity but the authors believe these individuals can be identified reliably with the Nephrotoxicity Risk Index using information available at vancomycin initiation. Further testing of the Nephrotoxicity Risk Index is ongoing. Cancer 1998;83:2597-2607. © 1998 American Cancer Society.

BACKGROUND Genetic factors are probably important in the development of gastric carcinoma in young patients (younger than 40 years). The authors investigated early onset primary gastric adenocarcinomas for the presence of microsatellite instability, which is a phenotypic marker for the hereditary nonpolyposis colon carcinoma syndrome. METHODS DNA was extracted from archival microdissected carcinoma and corresponding normal tissue from 10 British gastric carcinoma patients age 19 to 39 years at the time of diagnosis. A panel of 12 microsatellite loci were amplified by fluorescent polymerase chain reaction and analyzed using an automated DNA sequencer. RESULTS There was no evidence of microsatellite instability. In contrast, allelic imbalance was recorded at D3S966, D3S1076, D10S197, D11S904, P53, NM23, and DCC microsatellite loci. CONCLUSIONS The authors reported ten cases of early onset gastric carcinoma that demonstrated allelic imbalance but no evidence of instability at microsatellite loci. It is unlikely that defective DNA mismatch repair is important in this group of young patients. Cancer 1997; 79:684-7. © 1997 American Cancer Society.

BACKGROUND Dyspnea is the fourth most common symptom of patients who present to the emergency department (ED) at The University of Texas M. D. Anderson Cancer Center and may, in some patients with advanced cancer, represent a clinical marker for the terminal phase of their disease. This retrospective study describes the clinical characteristics of these patients, the resource utilization associated with the management of dyspnea, and the survival of patients with this symptom. METHODS The authors randomly selected 122 of 1068 patients presenting with dyspnea for a retrospective analysis. The median age of the patients was 58 years (range, 23-90 years) and 53% were female. Underlying malignancies were breast cancer (30%), lung cancer (37%), and other cancers (34%). Approximately 94% of the patients had received prior cancer treatment and the majority (69%) had uncontrolled, progressive disease. RESULTS The most common treatments administered in the ED were oxygen (31%), beta-2 agonists (14%), antibiotics (12%), and narcotics (11%). Approximately 60% of patients were admitted to the hospital from the ED for further treatment of dyspnea and the underlying malignancy, and the median length of stay was 9 days. The median overall survival after the ED visit for dyspnea was 12 weeks. Specific diagnoses were associated with different median survival rates: lung cancer patients: 4 weeks; breast cancer patients: 22 weeks (P = 0.0073, vs. lung cancer); and other cancer diagnoses: 27 weeks (P = 0.0027, vs. lung cancer). CONCLUSIONS Lung cancer patients presenting to the ED with dyspnea have much shorter survival than patients with other malignancies. For some patients, the presence of dyspnea requiring emergency treatment may indicate a phase in their illness in which resources should be shifted from acute intervention with hospitalization to palliative and supportive care measures. Cancer 1996;78:1314-9.

BACKGROUND. The diagnosis of melanomas at an early stage is associated with improved survival, so the recognition of changes in pigmented skin lesions over time is important. We have developed a computer imaging system with the aim of assisting clinicians in differentiating early melanomas from benign pigmented skin lesions. The objective of this study was to investigate the system's reliability over time in measuring diagnostic characteristics of pigmented skin lesions, including their color, size, shape, and distinctness of boundary. METHODS. We captured video images of 5 lesions, all larger than 2 mm in greatest dimension, on each of 66 Australian adolescents on 2 occasions approximately 1 month apart. Features extracted by computer image analysis included area, perimeter, and regularity of outline of the lesions, the mean and standard deviation of reflectance at red, green, and blue wavelengths, and the mean and standard deviation of the gradients of red, green, and blue reflectance at the lesion boundary. RESULTS. All measurements showed moderate to high reliability (intraclass correlation coefficients 0.66-0.94), except for the standard deviations of the color gradients, whose reliability improved to moderate levels (0.68-0.71) when the mean of 5 lesions was considered. For most outcomes, reasonable within subject reliability was achieved when five lesions per subject were measured. CONCLUSIONS. These results, in combination with previous work demonstrating tire reasonable ability of this computer imaging system to discriminate between malignant melanomas and other pigmented lesions, indicates that the system has the potential to become a useful tool for clinicians in following people with pigmented lesions over time to detect early malignant changes.

BACKGROUND Inadequate management of cancer related pain has resulted primarily from attitudinal barriers and a lack of knowledge about clinical assessment, the administration of analgesics, and therapeutic interventions. METHODS Fifty health-care providers (13 physicians, 21 nurses, and 16 pharmacists), working as a team, participated in a Role Model Program that presented principles of cancer pain management. A questionnaire that evaluated the fund of knowledge and attitudes regarding cancer pain management was administered prior to the 1-day workshop, at the end of the workshop, and at 4 and 12 months follow-up.[iu61] The workshop consisted of lectures and discussion groups; in the discussion groups, concepts were clarified, cases presented, and barriers to optimal cancer pain management identified. RESULTS Significant improvements in attitudes (P < 0.01), knowledge (P < 0.01), and total scores (P < 0.002) were observed when the preworkshop responses were compared with those obtained immediately after instruction. Scores on the questionnaire were the same or slightly better at both 4 and 12 months in follow-up, demonstrating no loss in acquired knowledge or attitude. Comparison of the postworkshop scores with those at 12 months follow-up were significantly better in attitude (P < 0.03), and in total score (P < 0.01); improvements in knowledge also approached significance (P < 0.06). These represented continuing improvements because significant differences in the attitude scores (P < 0.05) and the total score (P < 0.05) were observed when the 4-month and 12-month follow-up responses were evaluated. The effectiveness of the program in the transference of knowledge was also measured; in the first year of the program, more than 4500 health-care professionals were subsequently informed about cancer pain management from the Role Model Participants. CONCLUSIONS Significant improvements were observed immediately in both attitude and knowledge of cancer pain management principles after the 1-day Role Model Workshop. These improvements continued, as determined at 4 and 12 months follow-up. The Role Model Participants were highly motivated to share the learned principles of cancer pain management with other health-care professionals. These results are consistent with other Role Model Programs that both instruct and involve the participants. The Role Model Program is an efficient and effective means of educating health-care professionals in the concepts of cancer pain management. Cancer 1996;77:996-1001.

Primary lymphoma of the heart is an uncommon malignancy usually recognized at autopsy or fatal within a few weeks of diagnosis. Recently, it was reported in patients with acquired immune deficiency syndrome. A patient with diffuse large cell lymphoma of the heart is reported who had chest pain and rapidly evolving cardiac arrhythmias. The human immune deficiency virus antibody test was negative. Because of an aggressive diagnostic approach, therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone was started on the third day after diagnosis. The patient has survived 18 months with an objective response. To the authors' knowledge, this is the longest reported survival in primary cardiac lymphoma. The diagnosis in this patient was aided by excellent tumor delineation by nuclear magnetic resonance scanning. The authors believe that better survival in this patient was a result of prompt diagnosis and treatment because the behavior of the lymphoma was similar to aggressive lymphomas arising elsewhere.

Chemotherapy-induced nausea and emesis (CINE) is one of the most dreaded side effects of cancer therapy. To investigate the influence of these symptoms on a patient's quality of life (QOL), a validated tool measuring many domains is needed.A QOL questionnaire consisting of scales from the European Organization for Research and Treatment of Cancer QLQ-C30, the Morrow Assessment of Nausea and Emesis, the Osoba Nausea and Emesis Module, and new items specific to nausea, emesis, and retching was constructed and administered daily for 7-9 days to outpatients receiving emetogenic chemotherapy.Test-retest and internal consistency reliabilities ranged from 0.44 to 0.84 and from 0.59 to 0.85, respectively. Item and scale correlations indicated good convergent and discriminant validity. Scales and items measuring similar factors (e.g., severity of emesis and severity of nausea) had strong correlations than did scales measuring dissimilar factors (e.g., cognitive functioning and physical functioning). The validity of known groups was demonstrated by significant differences (P0.01) in patients' QOL scores between days with no episodes of nausea, emesis, or retching, days with 1 or 2 episodes, and days with more than 3 episodes. Patients' QOL significantly decreased as the number of episodes per day increased (P0.001).A CINE QOL questionnaire that successfully measures the short-term impact of nausea, emesis, and retching on patients receiving emetogenic chemotherapy has been developed, largely as a battery of preexisting questionnaires. The psychometric properties of the new questionnaire show adequate reliability and validity to warrant its use in clinical trials and outcomes studies. CINE adversely affects many domains within a patient's QOL.

BACKGROUND The correlation between platelet count and bleeding has been well described, although no formal methods for applying this information to clinical decisions are available. The authors developed a clinical prediction rule to guide the prophylactic use of platelet transfusions among patients with lymphoma or solid tumors. METHODS The Bleeding Risk Index (BRI) was developed from logistic regression analysis of a randomly selected 750-chemotherapy cycle derivation set using data from Day 1 of cycles. The sensitivity and specificity of a BRI-based prophylaxis strategy were compared in a 512-cycle validation set with two strategies based on initiation of prophylaxis when platelet counts fell below thresholds of 20,000 per μL or 10,000 per μL. RESULTS Factors that were predictive of bleeding included any prior episode of bleeding (odds ratio [OR], 5.6; 95% confidence interval [95% CI], 2.2–14.0), treatment with a drug affecting platelet function (OR, 5.1; 95% CI, 2.0–12.6), bone marrow metastases (OR, 4.3; 95% CI, 1.7–10.8), a baseline platelet count 2 (OR, 3.4; 95% CI, 1.4–8.5), and treatment with agents that were highly toxic to the bone marrow (OR, 2.2; 95% CI, 1.0–5.4). Compared with 20,000 and 10,000 platelet threshold strategies, the BRI-based strategy provided the best trade-off between sensitivity for major bleeding episodes (80%) and specificity for any bleeding (84%). CONCLUSIONS Patients with lymphoma or solid tumors who are at high risk of bleeding can be identified reliably on Day 1 of a chemotherapy cycle. An individualized, BRI-based approach to bleeding prophylaxis provides a highly sensitive and specific alternative to traditional, nonindividualized platelet threshold strategies. Cancer 2002;94:3252–62. © 2002 American Cancer Society. DOI 10.1002/cncr.10603

Despite advances in cardiopulmonary resuscitation and the education of its providers, survival remains dismal for cancer patients suffering in-hospital cardiac arrest. In an effort to determine if characteristics of cardiac arrest would represent a useful parameter for prognostication and recommendations regarding the suitability of ongoing resuscitation for various groups, this review was undertaken for patients who experienced in-hospital cardiac arrest.A retrospective study of data gathered between January 1993 and December 1997 was undertaken in a 518-bed comprehensive cancer center. The records of 243 inpatients who experienced cardiac arrest and received cardiopulmonary resuscitation were reviewed, and their course observed until hospital discharge or death.Sixteen of 73 patients (22%) who had sudden, unanticipated cardiac arrests survived to be discharged from the hospital; however, none (0 of 171) of the patients who experienced an anticipated cardiac arrest survived (P0.001). Logistic regression analysis revealed that anticipated cardiac arrest associated with metabolic derangement was an independent predictor of hospital mortality.Patients experiencing an anticipated cardiac arrest, the course of which could not be interrupted through aggressive management in an intensive care unit, have an extremely poor prognosis. Ongoing resuscitative measures in these patients need not be routinely provided. The authors suggest an algorithm for resuscitation that evaluates the characteristics of the arrest as a prognostic factor. This algorithm should be implemented once progressive deterioration spirals toward cardiac arrest that cannot be prevented. Such an approach should avoid painful and costly interventions that are futile with the present techniques of cardiopulmonary resuscitation.

Discrepancies between the severity of toxicities reported in early clinical trials and recent clinical experience with vancomycin have led to confusion regarding the need for routine serum vancomycin level monitoring and discontinuation of vancomycin when toxicities occur. Therefore, the authors examined the incidence, outcomes, and predictive factors of vancomycin-associated toxicities in general oncology practice with the goal of developing clinically relevant prediction rules and guidelines.All 742 consecutive cancer patients who received vancomycin at a comprehensive cancer center during a 3-month period were followed prospectively for the development and outcome of phlebitis, rash, ototoxicity, and nephrotoxicity. Logistic regression was used to derive a multiple variable model of the risk of nephrotoxicity. A clinical prediction rule, the Nephrotoxicity Risk Score, was developed from the risk model and validated prospectively.Phlebitis occurred in 3% of patients (95% confidence interval [95% CI], 2-4%), predominantly those with recently inserted central venous catheters. Rashes occurred in 11% of patients (95% CI, 9-13%); however, all but 4 patients also were receiving beta-lactam antibiotics. Clinical evidence of ototoxicity developed in 6% of patients (95% CI, 4-9%) who were receiving vancomycin plus other ototoxic agents and only 3% of patients (95% CI, 2-5%) not receiving other ototoxic agents (P = 0.08). Nephrotoxicity occurred in 17% of patients (95% CI, 15-20%). Logistic regression revealed that factors associated with an increased risk of nephrotoxicity included administration of other mild to moderate (P = 0.01) or severely nephrotoxic agents (P0.001) or an acute physiology and chronic health evaluation (APACHE) score40 (P = 0.002). Elevated serum vancomycin peak levels did not reliably predict subsequent nephrotoxicity.Vancomycin-associated toxicities usually are mild and self-limiting. Some patients are at a significantly higher risk of nephrotoxicity but the authors believe these individuals can be identified reliably with the Nephrotoxicity Risk Index using information available at vancomycin initiation. Further testing of the Nephrotoxicity Risk Index is ongoing.

Genetic factors are probably important in the development of gastric carcinoma in young patients (younger than 40 years). The authors investigated early onset primary gastric adenocarcinomas for the presence of microsatellite instability, which is a phenotypic marker for the hereditary nonpolyposis colon carcinoma syndrome.DNA was extracted from archival microdissected carcinoma and corresponding normal tissue from 10 British gastric carcinoma patients age 19 to 39 years at the time of diagnosis. A panel of 12 microsatellite loci were amplified by fluorescent polymerase chain reaction and analyzed using an automated DNA sequencer.There was no evidence of microsatellite instability. In contrast, allelic imbalance was recorded at D3S966, D3S1076, D10S197, D11S904, P53, NM23, and DCC microsatellite loci.The authors reported ten cases of early onset gastric carcinoma that demonstrated allelic imbalance but no evidence of instability at microsatellite loci. It is unlikely that defective DNA mismatch repair is important in this group of young patients.

Dyspnea is the fourth most common symptom of patients who present to the emergency department (ED) at The University of Texas M. D. Anderson Cancer Center and may, in some patients with advanced cancer, represent a clinical marker for the terminal phase of their disease. This retrospective study describes the clinical characteristics of these patients, the resource utilization associated with the management of dyspnea, and the survival of patients with this symptom.The authors randomly selected 122 of 1068 patients presenting with dyspnea for a retrospective analysis. The median age of the patients was 58 years (range, 23-90 years) and 53% were female. Underlying malignancies were breast cancer (30%), lung cancer (37%), and other cancers (34%). Approximately 94% of the patients had received prior cancer treatment and the majority (69%) had uncontrolled, progressive disease.The most common treatments administered in the ED were oxygen (31%), beta-2 agonists (14%), antibiotics (12%), and narcotics (11%). Approximately 60% of patients were admitted to the hospital from the ED for further treatment of dyspnea and the underlying malignancy, and the median length of stay was 9 days. The median overall survival after the ED visit for dyspnea was 12 weeks. Specific diagnoses were associated with different median survival rates: lung cancer patients: 4 weeks; breast cancer patients: 22 weeks (P = 0.0073, vs. lung cancer); and other cancer diagnoses: 27 weeks (P = 0.0027, vs. lung cancer).Lung cancer patients presenting to the ED with dyspnea have much shorter survival than patients with other malignancies. For some patients, the presence of dyspnea requiring emergency treatment may indicate a phase in their illness in which resources should be shifted from acute intervention with hospitalization to palliative and supportive care measures.

The diagnosis of melanomas at an early stage is associated with improved survival, so the recognition of changes in pigmented skin lesions over time is important. We have developed a computer imaging system with the aim of assisting clinicians in differentiating early melanomas from benign pigmented skin lesions. The objective of this study was to investigate the system's reliability over time in measuring diagnostic characteristics of pigmented skin lesions, including their color, size, shape, and distinctness of boundary.We captured video images of 5 lesions, all larger than 2 mm in greatest dimension, on each of 66 Australian adolescents on 2 occasions approximately 1 month apart. Features extracted by computer image analysis included area, perimeter, and regularity of outline of the lesions, the mean and standard deviation of reflectance at red, green, and blue wavelengths, and the mean and standard deviation of the gradients of red, green, and blue reflectance at the lesion boundary.All measurements showed moderate to high reliability (intraclass correlation coefficients 0.66-0.94), except for the standard deviations of the color gradients, whose reliability improved to moderate levels (0.68-0.71) when the mean of 5 lesions was considered. For most outcomes, reasonable within subject reliability was achieved when five lesions per subject were measured.These results, in combination with previous work demonstrating the reasonable ability of this computer imaging system to discriminate between malignant melanomas and other pigmented lesions, indicates that the system has the potential to become a useful tool for clinicians in following people with pigmented lesions over time to detect early malignant changes.

Inadequate management of cancer related pain has resulted primarily from attitudinal barriers and a lack of knowledge about clinical assessment, the administration of analgesics, and therapeutic interventions.Fifty health-care providers (13 physicians, 21 nurses, and 16 pharmacists), working as a team, participated in a Role Model Program that presented principles of cancer pain management. A questionnaire that evaluated the fund of knowledge and attitudes regarding cancer pain management was administered prior to the 1-day workshop, at the end of the workshop, and at 4 and 12 months follow-up. The workshop consisted of lectures and discussion groups; in the discussion groups, concepts were clarified, cases presented, and barriers to optimal cancer pain management identified.Significant improvements in attitudes (P0.01), knowledge (P0.01), and total scores (P0.002) were observed when the preworkshop responses were compared with those obtained immediately after instruction. Scores on the questionnaire were the same or slightly better at both 4 and 12 months in follow-up, demonstrating no loss in acquired knowledge or attitude. Comparison of the postworkshop scores with those at 12 months follow-up were significantly better in attitude (P0.03), and in total score (P0.01); improvements in knowledge also approached significance (p0.06). These represented continuing improvements because significant differences in the attitude scores (P0.05) and the total score (P0.05) were observed when the 4-month and 12-month follow-up responses were evaluated. The effectiveness of the program in the transference of knowledge was also measured; in the first year of the program, more than 4500 health-care professionals were subsequently informed about cancer pain management from the Role Model Participants.Significant improvements were observed immediately in both attitude and knowledge of cancer pain management principles after the 1-day Role Model Workshop. These improvements continued, as determined at 4 and 12 months follow-up. The Role Model Participants were highly motivated to share the learned principles of cancer pain management with other health-care professionals. These results are consistent with other Role Model Programs that both instruct and involve the participants. The Role Model Program is an efficient and effective means of educating health-care professionals in the concepts of cancer pain management.

Background. This study evaluated the perceptions of patients with breast cancer of their medical interactions with providers. The determinants and psychological consequences of communication problems also were examined. Methods. Ninety-seven patients with Stage I or II breast cancer completed a set of validated questionnaires before initiating postoperative therapy. Data on psychological distress were collected at baseline and 3-month follow-up, and multivariate models were fit to explain the relationship between pretreatment communication problems and subsequent psychological distress. Data on clinical variables were abstracted from medical records. Results. A substantial proportion of patients (84%) reported difficulties communicating with the medical team. Communication problems were more common among patients who were less optimistic about their disease and had less assertive coping styles. Patient-reported communication problems were associated with increased anxiety, depression, anger, and confusion at the 3-month follow-up. The association between communication problems and mood disturbance remained significant, although small, after adjusting for baseline mood disturbance, demographic, clinical, and coping style variables. Conclusion. Interventions that enhance communication between patients with breast cancer and their providers may improve patients' psychological adjustment to treatment. Conversely, interventions that lower distress and modify coping style may enhance communication.

Between May 1977 and April 1980, 238 patients with operable breast cancer were treated with adjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) chemotherapy. All patients were randomized to receive FAC alone or FAC with nonspecific immunotherapy with Bacillus Calmette-Guerin (BCG) vaccine. A randomization for routine postoperative irradiation was included in the study in May 1978. At the median follow-up of 33 months, 53 patients had developed recurrent disease. Up to the present time, there have been no significant differences in the disease-free survival of patients treated with FAC alone from those treated with FAC + BCG (P = 0.21). The disease-free survival for patients treated with and without routine postoperative irradiation was similar (P = 0.99). Disease-free survival of premenopausal and postmenopausal women was similar. The overall estimate of disease-free survival was 72% at 3 years.

The relationship of colorectal carcinoma with polyps was studied retrospectively in 1202 patients. The incidence of synchronous carcinoma (SC) and metachronous carcinoma (MC), prognosis, and recurrence patterns were studied. Synchronous polyps (SP) were found in 36% of the patients. SC was found in 4.4% of the patients, and MC developed in 3.5% of patients. The incidence of SC and of MC increased with SP, and varied according to number, size, and histologic features of the polyps. The adjusted 5-year survival rate was improved in patients with SP compared with those without SP, both overall (79% versus 64%, respectively) and by Dukes' Stage B (87% versus 73%, respectively) and Dukes' Stage C (56% versus 39%, respectively). The pattern of relapse was the same for the SP and non-SP groups. Subtotal colectomy is recommended for colorectal carcinoma and SP in good-risk patients.

One hundred consecutive Stage IIIA and IIIB Hodgkin's disease patients were treated between July 1969 and September 1976, on a combined chemotherapy-radiotherapy program consisting of two courses of MOPP followed by radiotherapy to the mantle, abdomen, and pelvis. Eighty-eight patients completed radiotherapy to all disease sites. At the time of this analysis, the mean follow-up period for the 100 patients was 45 months; 70 patients had been followed three to seven years. Projected five-year survival and disease-free survival figures for the 100 patients were 80% and 68% respectively; corresponding results for the 88 patients were 90% and 78%. To determine whether any of the following prognostic factors influenced results for either the 100 or the 88 patients, survival curves were calculated for age, sex, constitutional symptoms, histopathology, method of staging, and status of the mediastinum. Other than age, none of these factors influenced survival significantly. However, disease-free survival figures were influenced adversely by mediastinal disease as well as age.

The optimal treatment for squamous and cloacogenic tumors of the anorectum is controversial. Radical surgery, limited surgery, and radiotherapy (XRT) are all potentially curative. This study was undertaken to determine which patients are candidates for each type of treatment and which would benefit from combined treatment. The records of 192 patients treated at this institution between 1954 and 1979 with the diagnosis of squamous or cloacogenic carcinoma of the anorectum were retrospectively reviewed. A subgroup of 132 patients undergoing abdominal perineal resection (APR) was analyzed to determine prognostic factors for these tumors. No survival difference was observed between the two histologic types (P = 0.51). Prognostic variables significant at P = 0.05 or better were sex, size, nodal status, and level of invasion. A new staging system is proposed that utilizes tumor size, invasion, grade, and nodal status. Actuarial 10-year survival was 100%, 76%, 29%, and 0% for Stages A, B, C and D, respectively (P values 0.22, 0.0007, and 0.01, respectively). Twelve patients undergoing APR received postoperative XRT; when compared by stage with APR alone no survival difference can be shown, although there is a trend towards fewer local recurrences. Of 26 patients (14 Stage B, 12 Stage C) receiving preoperative XRT (average 4000 R) before APR, 10 had inoperable tumors prior to XRT. All became operable. Eight patients had negative surgical margins and survival was equivalent stage for stage to the operable group (Stage B 78%, 5-year survival; Stage C 43%, 5-year survival). Eleven patients had no demonstrable primary tumor after XRT, although three had nodal metastasis. Five-year survival was 83% for this group. Thirty-one local recurrences were retreated for cure by surgery, XRT, or combination. Actuarial 5-year survival after retreatment was 38%. Thirty metachronous inguinal metastases were seen, 20 were retreated for cure, 18 by inguinal lymphadenectomy. Actuarial 5-year survival was 42%. Using a new staging system based on analysis of prognostic parameters for this disease, the outcome of combined surgery and XRT is compared. The efficacy of preoperative XRT for inoperable tumors is demonstrated. An appreciable salvage rate for local or inguinal recurrence was observed. Cancer 53:1285-1293, 1984.

Seventy-nine patients with Stages IE and IIE non-Hodgkin's lymphomas of the stomach were treated between 1953 and 1980. The histopathologic classification was as follows: diffuse large cell, 61 (of which 23 were immunoblastic sarcomas [plasmacytoid]); diffuse well-differentiated lymphocytic, 6; diffuse mixed, 1; undifferentiated non-Burkitt's, 1; nodular, 9; and unclassifiable, 1. Thirty-five patients had Stage IE disease and 44 had Stage IIE. Treatment modalities included surgery, radiotherapy, chemotherapy, and combinations thereof. Sixty-six patients had a laparotomy for diagnosis and/or management. Of these, only 42 had a gastrectomy. The stomach was considered to be unresectable in the other 24 patients. There were 5 postoperative deaths among 31 patients who had a laparotomy or gastrectomy at our institution. The overall 5-year actuarial survival was 56%; the disease-free survival was 54%. For patients with Stage IE disease the survival was 76%, and for those with Stage IIE, 42%. Promising results were obtained in 13 patients who were treated on a multimodality program consisting of four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus bleomycin (Bleo), which was alternated with involved field radiotherapy. All 13 patients had no evidence of disease as of this report. Only one patient had a relapse (Waldeyer's ring), and he was salvaged with radiotherapy. Six of these 13 were diagnosed by endoscopic biopsy and did not have a laparotomy, 3 were found to have unresectable disease at laparotomy, and 4 had a resection. Biopsy with the flexible fiberscope and treatment with CHOP-Bleo and radiotherapy can avoid the morbidity and mortality of gastrectomy.

Staging celiotomy was performed in 139 previously untreated patients with lymphogram negative Stage I and I1 Hodgkin's disease. Sixteen additional patients received definitive radiotherapy for symptomatic relief of upper torso disease prior to abdominal exploration. The overall incidence of positive abdominal findings for these two groups was 34.5% and 31.2%, respectively. Further analysis of the 139 previously untreated cases revealed notable differences in incidence of positive abdominal findings for stage, presentation, and specific histology. Stage I patients with upper cervical or inguinal presentations o r a lymphocytic predominance classification had negative celiotomies, as contrasted with a 43% incidence of positive abdominal findings in patients with supraclavicular presentations. In Stage I1 disease, the incidence of positive findings was related to the status of the mediastinum. For mediastinal presentations, the incidence was 33.3%, as compared to 48% for nonmediastinal presentations. To date, the number of relapses in celiotomy Stage I and I1 patients has been low regardless of whether or not prophylactic irradiation was administered to the major lymph-node-bearing regions of the upper and lower torso. Of 9 patients with progression, extranodal spread occurred as the first evidence of new disease in 4 patients. The implication of this finding is considered in a discussion on the influence of staging celiotomy in the management of Stage I and II patients with Hodgkin's disease.

A staging system, based upon the experience of 1215 patients, was published by the American Joint Committee Task Force on Soft Tissue Sarcoma in 1977. A subset of these patients, 594, was selected to study recurrence-free survival time. The authors found 331 patients with a recurrence within 5 years (100 local only, 123 metastatic only, and 108 local + metastatic); median months to recurrence was 9.7. Within 5 years, recurrence was clearly associated with mortality: among the 331 patients who experienced a recurrence, 245 died, whereas only 31 died among the 263 who had no recurrence. To further evaluate the utility of the published staging system, a multivariate analysis of five factors was carried out for 297 of the 594 patients (patients with unknown information for any one of these factors were excluded). Factors in addition to grade that exerted a significant influence on recurrence were: direct extension, symptoms, and location of tumor when survival was measured to the first of any recurrence, and tumor size, measuring survival to the first metastatic recurrence. It is therefore recommended that these factors be taken into account in staging this disease. Estimates of probable recurrence-free survival time based upon the multivariate model (Weibull) are also presented.

A hybrid radiofrequency heating system previously reported to produce highly focused heating patterns at less than or equal to 10 cm depth in phantom models was utilized to selectively heat hypervascular, heat resistant rabbit V-2 tumors implanted in the left hindlimb. Spheroidal heating patterns 3 to 4 cm in diameter with minimal temperatures of 43 degrees C to 46 degrees C in two non-field perturbing probes at opposing edges of the tumor were consistently produced; however, temperature maxima 0.5 +/- 0.4 to 8.6 +/- 5.9 degrees C above minimum target temperatures of 43 degrees C and 46 degrees C, respectively, were observed. This led to both tumor regressions and adjacent normal tissue damage in some animals. These findings suggest this system may have application to selective heating of deep seated tumors, but that problems related to accurate thermal mapping and to intratumor temperature distribution must first be resolved.

Fifty-three non-Hodgkin's lymphoma patients staged I, IE, II, and IIE after laparotomy, received involved field radiotherapy with or without adjunctive chemotherapy. These cases have been analyzed for survival, disease-free survival, sites of relapse, and subsequent management. For nodular lymphoma patients, the five-year survival figure was 87%. While this represents only modest improvement over survival figures for patients staged I and II by lymphangiography, results for patients with upper torso disease were significantly better. Although there was a definite incidence of relapse, early failures common in the lymphangiogram series, were not seen in this study. Of the total group of 14 patients, 4 relapsed after a minimum complete remission period of 20 months. The five-year survival figure for all presentations of stages I and II diffuse histiocytic lymphoma was 85%. This represents a substantial improvement over the corresponding figure of 36% for patients staged clinically after lymphangiography. The improvement in results is credited to more precise staging of patients with peripheral presentations, the use of adjunctive multiple-agent chemotherapy for abdominal and mediastinal presentations, and more effective treatment for relapse. To date, too few patients with peripheral presentations have been treated to determine the value of adjunctive chemotherapy for nodular or diffuse histiocytic patients.

From January 1963 through December 1977, 300 adults with soft-tissue sarcomas were treated by a conservative surgical excision and postoperative radiotherapy. The absolute two- and five-year disease-free survival rates are 74% (222/300) and 61.3% (103/168), respectively. The five-year survival rate varies with: (1) anatomic site, e.g., 69.4% (75/108) for extremity lesions vs. 33% (5/15) for abdominal lesions; (2) histopathologic diagnosis, e.g., 86.4% (19/22) for fibrosarcoma vs. 50% (15/30) for neurofibrosarcoma; and (3) stage of the lesion. The overall local recurrence rate was 22.3% (67/300) and 27% (81/300) of the patients developed distant metastases. The incidence of lymph node metastases as an initial site of spread was only 2.7% (8/300); therefore, elective treatment of the regional lymphatics is not indicated. The 6.5% incidence of significant complications in extremities is low and might be further diminished by careful treatment planning. The combination of conservative surgery and postoperative radiation therapy maintains a functional limb in 84.5% (169/200) of patients with extremity lesions. This rate is comparable to the five-year survival rate attained with radical surgery.

One hundred thirty-three consecutive, previously untreated patients who had metastatic breast cancer were treated with a combination of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). They were randomly assigned to receive nonspecific immunotherapy with a heptavalent pseudomonas vaccine. Sixty-five patients were treated with pseudomonas vaccine, whereas 68 did not receive immunotherapy. In addition, all patients with estrogen receptor-positive tumors or tumors with an estrogen receptor status were also treated with tamoxifen. To allow clinical assessment of hormone sensitivity in vivo, tamoxifen was started 6 weeks before chemotherapy except in patients who had life-threatening disease. After the initial 6 weeks of tamoxifen, 3% of patients had achieved a complete remission, 9% a partial remission, while 16% achieved a minor response. The maximum response after tamoxifen and chemotherapy included complete remissions in 20% of patients and partial remissions in 61% of patients for an overall remission rate of 81%. The median response duration was 15 months, and the median survival time, 27 months. There were no differences in remission rate, remission duration, or survival time between the groups treated with or without pseudomonas vaccine. Eleven patients with limited metastatic disease received radiotherapy consolidation to initially involved sites. In these patients the median time from radiotherapy to progression of disease was 33 months, and the median survival time was 46 months. We conclude that nonspecific immunotherapy with pseudomonas vaccine failed to increase remission rate or survival time. Furthermore, the addition of tamoxifen to FAC chemotherapy did not improve the remission rate or duration compared to a recent, historical control group of patients treated with only FAC chemotherapy.

Ninety patients with Stage 1 or 11, including extranodal (E), presentations of non-Hodkin's lymphoma were investigated by laparotomy, either for the definitive staging of patients with peripheral presentations or for diagnosis of abdominal disease. Sixty-eight patients had staging laparotomies after extensive work-up, which included lymphangiography and bone marrow biopsy. The remaining 22 patients had laparotomies for diagnosis of abdominal symptoms or for management of unrelated surgical problems, with lyphoma being found incidentally. The incidence of positive abdominal findings in the 68 patients who had staging laparotomies depended on histologic subtype. In nodular lymphoma patients, abdominal disease was found in 17 of 28 (61%) and in diffuse lymphoma patients, in 9 of 40 (22.5%). For patients with nodular lymphomas upstaged by laparotomy, the positive findings tended to cluster around an axis consisting of the celiac, porta-hepatic, para-aortic, and root of the mesentery lymph nodes. In addition, 64% of these patients had splenic involvement. For the diffuse lymphomas upstaged by laparotomy, the distribution of positive findings was similar to that of the nodular lymphoma group; however, only 1 patient had splenic involvement. By contrast, in approximately half of the diffuse lymphoma patients who had laparotomies for diagnosis, the gastrointestinal tract was found to be involved in addition to the previously cited lymph nodes. Cancer 452778-2786, 1980.

A retrospective review of 83 patients with Stage I-III Hodgkin's disease treated with an upper mantle field revealed a rate of radiation-related pericardial effusion (RRP) of 28.9% (24/83). Clinical presentation was asymptomatic effusion in 10/24 and symptomatic effusion in 14/24. RRP was self-limited in all but 4 patients, who progressed to chronic effusion requiring pericardiectomy (4/24). A midplane mediastinal dose of 4000 rads in 4 weeks was given with an anteriorly weighted mantle field that resulted in an average pericardial dose of 5325 rads (1823 ret) and an average midplane cardiac dose of 4625 rads (1558 ret). The rate of RRP was correlated with increasing degree of mediastinal Hodgkin's disease. Increased incidence of RRP with increasing cardiac and pericardial dose could not be proven statistically. Factors which may facilitate pericardial effusion following a basic radiation injury are discussed.

Radical dose radiation therapy alone or combined with limited surgery has been employed in the management of 100 patients with primary (71) and recurrent (29) sarcoma of soft tissue. Results of this experience show that a combination of conservative surgery and radiation therapy, based upon radical dose levels and sophisticated techniques, is effective: only 13 of 100 patients showed local regrowth during a followup of 2-12 years. This may be compared with an expected congruent to 25 recurrences had treatment been radical surgery (wide resection or amputation). For lesions located on the distal extremities (elbow-hand, knee-foot) there were local failures in only 3 of 59 (5 percent). Further, 75 percent of patients treated by the improved techniques utilized in the recent 8 years retained a useful limb which is free of pain or edema. Histopathologic grade is demonstrated to be an important indicator of prognosis of local recurrence and of disease-free survival. Local recurrence rates were 0/23, 9/53, and 4/24 for Grades 1, 2, and 3. Disease-free survival rates were 19/23 (86 percent), 27/53 (51 percent), and 4/24 (17 percent) for Grades 1, 2, and 3, respectively. Invasion of skin appeared to be a sign of poor prognosis; 8 of 9 such patients developed distant metastases.

Three hundred ten patients with Stage II or Stage III breast cancer were entered on an adjuvant protocol consisting of a combination of 5-fluorouracil, doxorubicin, cyclophosphamide, vincristine, and prednisone (FACVP). In the second phase of the study, patients with estrogen receptor-negative tumors received sequential courses of methotrexate and vinblastine. Other patients, who were estrogen receptor-positive or unknown, were randomized to receive either tamoxifen alone or tamoxifen plus methotrexate and vinblastine. All therapy was completed within 1 year. The estimated disease-free rate at 5 years was 68% among patients with Stage II disease and 52% for patients who had Stage III disease. Among patients with estrogen receptor-positive tumors, disease-free survival was significantly prolonged in patients who received methotrexate and vinblastine in addition to tamoxifen (P = 0.04). However, this difference was less pronounced when all randomized patients (including those whose estrogen receptor status was unknown) were included in the comparison. Although most patients experienced moderate to severe granulocytopenia, infectious complications were infrequent. One patient died of septicemia. Congestive heart failure developed in two patients, one of whom had a history of myocardial infarction and congestive heart failure.

One hundred seventy-four evaluable patients with noninflammatory Stage III (both operable and inoperable) breast cancer were treated with a combined modality strategy between 1974 and 1985. All patients received combination chemotherapy with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide (FAC) as their initial form of therapy. After three cycles of chemotherapy, local treatment in the form of a total mastectomy with axillary dissection, or radiotherapy, or both, was completed. Subsequently, adjuvant chemotherapy was continued. There were 48 patients with Stage IIIA, and 126 patients with Stage IIIB disease. A complete remission was achieved in 16.7% of the patients, and 70.7% achieved a partial remission after the initial three cycles of FAC. The complete response rate was higher for patients with Stage IIIA, than for patients with Stage IIIB disease. All but six of the 174 patients treated were rendered disease-free after induction chemotherapy and local treatment. The median follow-up of this group of patients is 59 months. The 5-year disease-free survival rates were 84% for patients with Stage IIIA, and 33% for patients with Stage IIIB disease. The 5-year survival rate for, patients with Stage IIIA was 84%, and for patients with Stage IIIB 44%. At 10 years, 56% of patients with Stage IIIA and 26% of patients with Stage IIIB disease are projected to be alive. Younger patients, and those with estrogen receptor-positive tumors, had a trend for better survival than older patients and those with estrogen receptor-negative tumors. The quality of response to induction chemotherapy correlated prominently with prognosis, as did compliance with treatment. Twenty-six patients (15.3%) had locoregional recurrence. This multidisciplinary approach to locally advanced breast cancer rendered most patients disease-free and produced an excellent local control rate. Modifications of this treatment strategy may result in further improvement of survival rates.

Results of management of 57 patients with sarcoma of soft tissue on an extremity by radical dose radiation therapy are presented. These patients had been treated 2 to 10 years previously at the University of Texas M.D. Anderson Hospital. Forty-six patients were seen after simple excision (no palpable tumor at time of our examination), while 11 patients were treated for the primary or a recurrent tumor. The recommended surgical treatment was amputation in all patients of this study sample. Radiation therapy technique was complex; dose level was 6300–7000 rads or the equivalent in 61/2-7 weeks. Local control has been achieved in 50 of 57 patients. For the 46 patients with lesions in the elbow-hand or knee-foot regions, local control has been 100%. In contrast, 7 of 11 tumors located in the proximal extremities (upper arm or thigh) have recurred locally. A useful limb has been retained for 2 to 10 years in 34 of the cases. The more refined techniques of therapy now being employed yield a good functional result in nearly all cases. Metastasis-free survival at 2 to 10 years is 58%. This figure depends not only upon histologic type but apparently also on histologic grade: 26 of 36 (72%) for Grades 1 and 2 but only 7 of 17 (41%) for Grade 3.

Chondrosarcoma cells obtained from the tumor of one patient were established in culture. The tumor cells contained filamentous structures resembling viral ribonucleoprotein strands. Autologous small lymphocytes reacted immediately with cultured tumor cells and inhibited the growth of the culture. Destruction of tumor cells by lymphocytes was seen; autologous fibroblasts were not damaged. Small lymphocytes of another patient with chondrosarcoma also reacted immediately with cultured allogeneic tumor cells and inhibited growth. Lymphocytes of normal donors reacted both with cultured fibroblastic and neoplastic cells of the patient but only after several days of co-cultivation; blastic transformation of lymphocytes was evident during co-cultivation. It is proposed that patients with chondrosarcoma circulate presensitized small “executor” lymphocytes committed to a tumor antigen. The patient's serum reacted with cytoplasmic antigens of the autologous tumor cells in an indirect fluorescent antibody test.

A system for staging the clinical status of patients with soft tissue sarcomas is presented, based on the clinical characteristics of the primary tumor (size, extension), the involvement of lymph nodes, the presence of metastases, and the grade of the tumor. This represents the TNM system with grade of tumor (G) added. The system evolved was based on examination of 1215 cases of 13 types of soft tissues sarcomas, primarily in the extremities (fibrosarcoma, liposarcoma, etc.). Nine stages are described, and they are correlated with survival in the cases reviewed. The staging system now can be used for case evaluation for therapy determination and for intercomparison of series of patients as to incidence of different kinds of tumors, effects of treatment, and survival.

The optimal treatment for squamous and cloacogenic tumors of the anorectum is controversial. Radical surgery, limited surgery, and radiotherapy (XRT) are all potentially curative. This study was undertaken to determine which patients are candidates for each type of treatment and which would benefit from combined treatment. The records of 192 patients treated at this institution between 1954 and 1979 with the diagnosis of squamous or cloacogenic carcinoma of the anorectum were retrospectively reviewed. A subgroup of 132 patients undergoing abdominal perineal resection (APR) was analyzed to determine prognostic factors for these tumors. No survival difference was observed between the two histologic types (P = 0.51). Prognostic variables significant at P = 0.05 or better were sex, size, nodal status, and level of invasion. A new staging system is proposed that utilizes tumor size, invasion, grade, and nodal status. Actuarial 10-year survival was 100%, 76%, 29%, and 0% for Stages A, B, C and D, respectively (P values 0.22, 0.0007, and 0.01, respectively). Twelve patients undergoing APR received postoperative XRT; when compared by stage with APR alone no survival difference can be shown, although there is a trend towards fewer local recurrences. Of 26 patients (14 Stage B, 12 Stage C) receiving preoperative XRT (average 4000 R) before APR, 10 had inoperable tumors prior to XRT. All became operable. Eight patients had negative surgical margins and survival was equivalent stage for stage to the operable group (Stage B 78%, 5-year survival; Stage C 43%, 5-year survival). Eleven patients had no demonstrable primary tumor after XRT, although three had nodal metastasis. Five-year survival was 83% for this group. Thirty-one local recurrences were retreated for cure by surgery, XRT, or combination. Actuarial 5-year survival after retreatment was 38%. Thirty metachronous inguinal metastases were seen, 20 were retreated for cure, 18 by inguinal lymphadenectomy. Actuarial 5-year survival was 42%. Using a new staging system based on analysis of prognostic parameters for this disease, the outcome of combined surgery and XRT is compared. The efficacy of preoperative XRT for inoperable tumors is demonstrated. An appreciable salvage rate for local or inguinal recurrence was observed.

One hundred thirty-three consecutive, previously untreated patients who had metastatic breast cancer were treated with a combination of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). They were randomly assigned to receive nonspecific immunotherapy with a heptavalent pseudomonas vaccine. Sixty-five patients were treated with pseudomonas vaccine, whereas 68 did not receive immunotherapy. In addition, all patients with estrogen receptor-positive tumors or tumors with an estrogen receptor status were also treated with tamoxifen. To allow clinical assessment of hormone sensitivity in vivo, tamoxifen was started 6 weeks before chemotherapy except in patients who had life-threatening disease. After the initial 6 weeks of tamoxifen, 3% of patients had achieved a complete remission, 9% a partial remission, while 16% achieved a minor response. The maximum response after tamoxifen and chemotherapy included complete remissions in 20% of patients and partial remissions in 61% of patients for an overall remission rate of 81%. The median response duration was 15 months, and the median survival time, 27 months. There were no differences in remission rate, remission duration, or survival time between the groups treated with or without pseudomonas vaccine. Eleven patients with limited metastatic disease received radiotherapy consolidation to initially involved sites. In these patients the median time from radiotherapy to progression of disease was 33 months, and the median survival time was 46 months. We conclude that nonspecific immunotherapy with pseudomonas vaccine failed to increase remission rate or survival time. Furthermore, the addition of tamoxifen to FAC chemotherapy did not improve the remission rate or duration compared to a recent, historical control group of patients treated with only FAC chemotherapy.