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Biomedical subjects

A B Kornblith

Publications and source records attributed to A B Kornblith.

At least 37 records · Page 2Linked to original sources

Quality of life of women with ovarian cancer.

The primary objectives of this study were to determine the nature and extent of physical problems and psychological distress experienced by women with ovarian cancer and to identify medical and sociodemographic factors that were predictive of distress. Quality of life was assessed at 3-month intervals, for a maximum of 12 months in 151 ovarian cancer patients, most with advanced-stage disease (86%). Patients' pain, other physical symptoms, level of physical functioning, psychological state, and social functioning were evaluated using the following measures: a detailed pain questionnaire, Memorial Pain Assessment Card, Memorial Symptom Assessment Scale, Mental Health Inventory (MHI), Functional Living Index--Cancer (FLIC), and the Karnofsky Performance Status. Upon entry, 33% of patients reported significant psychological distress, as indicated by MHI Psychological Distress scores (MHI-PD) equal or greater to 1.5 standard deviations above the mean of a nationwide community sample. Impaired physical functioning (FLIC subscale) was the most important predictor of heightened psychological distress (MHI-PD) at baseline (1.5 SD or greater above the norm) (P = 0.0004) in a stepwise logistic regression involving medical/physical and sociodemographic variables as predictors. Further, significant differences were found in all quality of life scales between patients with Karnofsky Performance Status scores of < or = 80, and those with ratings of 90 or greater (P = 0.036 to P < 0.0001). These data suggest the need for an improved and more frequent assessment of ovarian cancer patients' psychological status, particularly as physical functioning declines, to improve early detection and referral to treatment of those suffering from psychiatric sequelae of cancer.

Adult↗

Pain in ovarian cancer patients. Prevalence, characteristics, and associated symptoms.

BACKGROUND: The prevalence, characteristics, and impact of pain and other symptoms have not been studied systematically in women with ovarian cancer. Anecdotally, pain has been associated with the onset of the disease and is a common problem among those with advanced cancer; symptoms other than pain appear to be highly prevalent. Given the profound influence of pain and other symptoms on quality of life, the evaluation of these phenomena could provide data relevant to the clinical management of these patients and advance quality of life research in the area of symptom assessment. METHODS: Questionnaires were completed by 111 inpatients and 40 outpatients with ovarian cancer who were undergoing treatment at a cancer center. Measures included a comprehensive pain questionnaire; the Rand Mental Health Inventory, Functional Living Index--Cancer; and the Memorial Symptom Assessment Scale. RESULTS: The sample (N = 151) represented 74% of the eligible patients. The median age was 55 years (range, 23-86), 82% had Stage III or IV disease at presentation, and 69% had active disease at the time of the survey. Pain, fatigue, and psychologic distress were the most prevalent symptoms. Sixty-two percent (N = 94) described a pain syndrome that preceded the onset or recurrence of the disease, and 42% (N = 63) reported "persistent or frequent pain" during the preceding 2 weeks. The latter pain had a median duration of 2 weeks (range, less than 1 to 756 weeks) and usually was in the abdominopelvic region (80%), frequent or almost constant (66%), and moderate to severe. Most patients reported moderate or greater pain-related interference with various aspects of function, particularly activity (68%), mood (62%), work (62%), and overall enjoyment of life (61%). Performance status, inpatient status, and unmarried status were significant predictors of pain presence or intensity, and both performance status and extent of tumor were significant predictors of pain interference with function. CONCLUSIONS: Among those with ovarian cancer, greater than 40% experienced pain that substantially undetermined function in one half to two thirds of these patients. Impaired performance status is associated most strongly with pain. The onset or recurrence of disease often is heralded by a stereotypic pain syndrome.

Adult↗

Quality of life of patients with prostate cancer and their spouses. The value of a data base in clinical care.

BACKGROUND: Because of the dearth of information concerning the quality of life of patients with prostate cancer, a data base was established to examine the nature and extent of problems in patients' and spouses' adaptation and their interrelationships and to examine the effect of disease stage combined with treatment regimen on patients' quality of life. METHODS: One hundred seventy-two patients and 83 spouses/partners completed quality of life questionnaires in a prostate cancer health education lecture series. The measures used were the European Organization for Research and Treatment of Cancer (EORTC) Prostate Cancer Quality of Life Questionnaire, the Intrusion subscale (IS) of the Impact of Event Scale; and Selby's QL Uniscale. Fifty-five percent of patients had received medical and/or surgical hormonal therapy, 28% had received a radical prostatectomy and/or radiation therapy only, and 18% had not been placed on any treatment. RESULTS: Patients experiencing problems in adaptation were significantly more likely to have advanced stage disease; received surgical or medical hormonal therapy; and were reporting greater pain, fatigue, urinary problems, and deteriorating physical functioning. Spouses reported significantly greater psychological distress than did patients (EORTC Psychological Distress subscale, P < 0.001; IS, P < 0.001). CONCLUSIONS: A two-stage clinical evaluation is recommended, in which quality of life questionnaires would initially be used to identify patients and spouses experiencing problems in adaptation for further evaluation by a mental health professional for appropriate treatment.

Adaptation, Psychological↗

Symptom prevalence, characteristics and distress in a cancer population.

Despite the importance of symptom control in the cancer population, few studies have systematically assessed the prevalence and characteristics of symptoms or the interactions between various symptom characteristics and other factors related to quality of life (QOL). As part of a validation study of a new symptom assessment instrument, inpatients and outpatients with prostate, colon, breast or ovarian cancer were evaluated using the Memorial Symptom Assessment Scale and other measures of psychological condition, performance status, symptom distress and overall quality of life. The mean age of the 243 evaluable patients was 55.5 years (range 23-86 years); over 60% were women and almost two-thirds had metastatic disease. The Karnofsky Performance Status (KPS) score was < or = 80 in 49.8% and 123 were inpatients at the time of assessment. Across tumour types, 40-80% experienced lack of energy, pain, feeling drowsy, dry mouth, insomnia, or symptoms indicative of psychological distress. Although symptom characteristics were variable, the proportion of patients who described a symptom as relatively intense or frequent always exceeded the proportion who reported it as highly distressing. The mean (+/- SD range) number of symptoms per patient was 11.5 +/- 6.0 (0-25); inpatients had more symptoms than outpatients (13.5 +/- 5.4 vs. 9.7 +/- 6.0, p < 0.002) and those with KPS < or = 80 had more symptoms than those with KPS > 80 (14.8 +/- 5.5 vs. 9.2 +/- 4.9, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress.

The Memorial Symptom Assessment Scale (MSAS) is a new patient-rated instrument that was developed to provide multidimensional information about a diverse group of common symptoms. This study evaluated the reliability and validity of the MSAS in the cancer population. Randomly selected inpatients and outpatients (n = 246) with prostate, colon, breast or ovarian cancer were assessed using the MSAS and a battery of measures that independently evaluate phenomena related to quality of life. Symptom prevalence in the 218 evaluable patients ranged from 73.9% for lack of energy to 10.6% for difficulty swallowing. Based on a content analysis, three symptoms were deleted and two were added; the revised scale evaluates 32 physical and psychological symptoms. A factor analysis of variance yielded two factors that distinguished three major symptom groups and several subgroups. The major groups comprised psychological symptoms (PSYCH), high prevalence physical symptoms (PHYS H), and low prevalence physical symptoms (PHYS L). Internal consistency was high in the PHYS H and PSYCH groups (Cronback alpha coefficients of 0.88 and 0.83, respectively), and moderate in the PHYS L group (alpha = 0.58). Although the severity, frequency and distress dimensions were highly intercorrelated, canonical correlations and other analyses demonstrated that multidimensional assessment (frequency and distress) augments information about the impact of symptoms. High correlations with clinical status and quality of life measures support the validity of the MSAS and indicate the utility of several subscale scores, including PSYCH, PHYS, and a brief Global Distress Index. The MSAS is a reliable and valid instrument for the assessment of symptom prevalence, characteristics and distress. It provides a method for comprehensive symptom assessment that may be useful when information about symptoms is desirable, such as clinical trials that incorporate quality of life measures or studies of symptom epidemiology.

Adult↗

Quality of life in patients with limited small-cell carcinoma of the lung receiving chemotherapy with or without radiation therapy, for cancer and leukemia group B.

Quality of life was assessed in 57 patients with limited small-cell carcinoma of the lung utilizing psychological scales that measured mood, functional status, and cognitive impairment. These patients received chemotherapy with or without radiotherapy to the primary tumor. All patients received prophylactic cranial radiation. Patients who received the combination of chemotherapy and radiotherapy to both the primary tumor and CNS had an increase in overall survival. However, because of the increased toxicity experienced by these patients, a decrease in quality of life was documented by measures of psychological distress when compared to patients receiving chemotherapy alone. The findings support the importance of utilizing quality of life measures in addition to measures of physical toxicity so that patients can make an informed choice regarding treatment options.

Activities of Daily Living↗

Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B.

PURPOSE: To assess the chemotherapy regimen of cisplatin, vinblastine, and hydrazine sulfate administered to patients with non-small-cell lung cancer (NSCLC) in a randomized, placebo-controlled double-blind phase III study. PATIENTS AND METHODS: Between July 25, 1989 and February 1, 1991, 291 patients with stage IIIB or IV NSCLC and performance status 0 or 1 were randomized to receive cisplatin 100 mg/m2 intravenously (IV) every 28 days, vinblastine 5 mg/m2 IV per week times five, then every 2 weeks; and either hydrazine sulfate 60 mg three times per day orally or placebo. The concurrent use of corticosteroids, medroxyprogesterone, or other appetite stimulants was not permitted. Treatment groups were comparable for known prognostic variables. The primary end point of this study was survival; however, the influence of hydrazine sulfate on nutritional status, performance status, and quality of life was also assessed. RESULTS: Analysis of 266 eligible patients showed a median survival duration of 7.78 months for the hydrazine sulfate-treated group compared with 7.70 months for the placebo-treated group (P = .65, log-rank). Objective response rates were similar for the two groups, with 4% complete responses, 20% partial responses, and 2% regressions in those treated with hydrazine sulfate; 3% complete responses, 23% partial responses, and 2% regressions in those who received placebo. The major toxicity was severe or life-threatening neutropenia, which occurred in 65% of hydrazine sulfate patients and 63% of placebo patients. There were no differences noted between the two groups in degree of anorexia, weight gain or loss, or overall nutritional status. Sensory and motor neuropathy occurred significantly more often in patients treated with hydrazine sulfate. Quality of life was significantly worse in patients who received hydrazine sulfate. CONCLUSION: This study suggests no benefit from the addition of hydrazine sulfate to an effective cytotoxic regimen.

Antineoplastic Combined Chemotherapy Protocols↗

A comparison of the quality of life of patients with metastatic prostate cancer who received or did not receive hormonal therapy.

BACKGROUND AND METHODS: The quality of life in patients who elected to receive hormonal therapy for newly diagnosed asymptomatic metastatic prostate cancer was compared with a comparable group of patients who chose to defer immediate intervention. RESULTS AND CONCLUSIONS: The premise that active therapy, despite its side effects, would improve or maintain the psychosocial quality of life was not substantiated, and the no-therapy group had better physical and sexual functioning.

Aged↗

Effect of megestrol acetate on quality of life in a dose-response trial in women with advanced breast cancer. The Cancer and Leukemia Group B.

PURPOSE: The impact of the side effects of megestrol acetate on the quality of life of noncachectic women with advanced breast cancer was studied in a dose-response clinical trial of the Cancer and Leukemia Group B (CALGB 8741). Side effects of appetite increase and weight gain at higher doses were predicted to have a negative effect on quality of life. PATIENTS AND METHODS: Stage IV breast cancer patients were randomized to receive either 160, 800, or 1,600 mg/d of megestrol acetate. Quality of life was assessed in 131 patients at trial entry and at 1 and 3 months while on treatment, by telephone interview, using the following measures: the Functional Living Index-Cancer (FLIC), Rand Functional Limitations Scale, Rand Mental Health Inventory (MHI), the Body Image Subscale, and linear analog scales of drug side effects. RESULTS: At 3 months, women treated with 160 mg/d reported less severe side effects (P < .0005), better physical functioning (FLS, P < .0005), less psychologic distress (MHI, P = .008), and an improvement in overall quality of life (FLIC, P = .003) from the time of study entry as compared with those treated with 1,600 mg/d. Patients who received the 800-mg/d dose fell between the low- and high-dose arms in reported intensity of drug side effects, but responded similarly to those in the 160-mg/d group in terms of physical functioning, psychologic distress, and overall quality of life. CONCLUSION: Unless additional follow-up data demonstrate a survival advantage at higher doses, the 160-mg/d dose is optimal, achieving maximal treatment effect with the fewest side effects and better quality of life.

Appetite↗

Comparison of psychosocial adaptation and sexual function of survivors of advanced Hodgkin disease treated by MOPP, ABVD, or MOPP alternating with ABVD.

BACKGROUND: Survivors of advanced Hodgkin disease, who were assigned randomly to treatment by mechlorethamine, vincristine, procarbazine, and prednisone (MOPP); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); or MOPP alternating with ABVD in a clinical trial of the Cancer and Leukemia Group B (protocol 8251), were compared in terms of their psychosocial adaptation and psychosexual function an average of 2.2 years after completion of treatment (range, 1-5 years). The study was undertaken to determine if there were differences among treatments in these functional areas as a consequence of differential long-term gonadal damage in the three regimens. METHODS: Ninety-three disease-free survivors of advanced Hodgkin disease (56 men and 37 women) were studied (a minimum of 1 year after completion of treatment) by an interview conducted over the telephone. Standardized measures were used to assess their psychologic, sexual, family, and vocational functioning, including the following tests: the Psychosocial Adjustment to Illness Scale--Self Report, the Brief Symptom Inventory, the Profile of Mood States, and the Impact of Event Scale. RESULTS: Contrary to expectation, no statistically significant differences in survivors' psychosocial adaptation or psychosexual function were found by treatment arm. Infertility (based on survivors' reports of medical test results and perceptions) and lower income 1 year before the diagnosis of cancer were significant predictors of poorer adjustment. Most survivors reported a range of problems that they attributed to having had cancer: 35%, proven or perceived infertility; 24%, sexual problems; 31%, health and life insurance problems; 26%, a negative socioeconomic effect; and 51%, conditioned nausea, associated with visual or olfactory reminders of chemotherapy. CONCLUSIONS: No significant long-term advantage in psychosocial adaptation or psychosexual function was found for survivors of Hodgkin disease treated by the less gonadally toxic ABVD regimen 1 to 5 years after completion of treatment.

Adaptation, Psychological↗

Hodgkin disease survivors at increased risk for problems in psychosocial adaptation. The Cancer and Leukemia Group B.

BACKGROUND: The long-term psychosocial adaptations of 273 survivors of advanced Hodgkin disease were assessed to determine the nature and extent of problems experienced and to identify those at high risk for maladaptation. METHODS: Hodgkin disease survivors were identified who initially had been treated in clinical trials within the Cancer and Leukemia Group B from 1966 to 1986, were currently disease free, and had completed treatment for a minimum of 1 year. All survivors had advanced Hodgkin disease (with disease diagnosed at a mean age of 28 years). Survivors were at a mean age of 37 years at the time of interview (6.3 years after treatment completion), and 60% were male. Survivors were interviewed over the telephone 7-10 days after questionnaires were mailed to them concerning their psychological, social, vocational, and sexual functioning. RESULTS: Psychological distress was found to be elevated by one standard deviation (SD) above that of healthy subjects on the Brief Symptom Inventory, and 22% met the criterion suggested for a psychiatric diagnosis. In addition, the following problems were reported by survivors to be a consequence of having had Hodgkin disease: denial of life (31%) and health (22%) insurance, sexual problems (37%), conditioned nausea in response to reminders of chemotherapy (39%), and a negative socioeconomic effect (36%). Survivors found to be at high risk for maladaptation were: men earning less than $15,000 per year or who were currently unemployed; unmarried individuals; those with serious illnesses since treatment completion; and those who were less educated. CONCLUSIONS: These findings suggest that including a routine assessment of these factors would help to target survivors in need of additional evaluation and treatment.

Adaptation, Psychological↗

Quantitative changes in tumor metabolism, partial pressure of oxygen, and radiobiological oxygenation status postradiation.

Hypoxia is considered to be a major cause of tumor radioresistance. Reoxygenation of previously hypoxic areas after a priming dose of radiation is associated with an increase in tumor radiosensitivity. In a study of a hypoxic mammary carcinoma, 31P nuclear magnetic resonance spectra showed statistically significant increases in metabolite ratios (phosphocreatine/Pi and nucleotide triphosphate/Pi) after 65 and 32 Gy. The maximum changes in metabolite ratios after 32 Gy occurred at 48 h, although significant changes were detected at 24 h. A corresponding increase in the mean tumor pO2 (polarographic microelectrode measurements) and a decrease in hypoxic cell fraction [changes in paired (clamped versus unclamped) tumor control dose for 50% of tumors] were also shown to occur 48 h after a priming dose of 32 Gy. A significant increase in the mean tumor pO2, phosphocreatine/Pi, and nucleotide triphosphate/Pi, compared to initial values, was noted at 24, 48, and 96 h post 65-Gy radiation. An increase in the downfield component of the phosphomonoester peak relative to the upfield component (phosphoethanolamine), is also noted after doses of 65 and 32 Gy. These are likely to be due to cell kill and/or decreased cell proliferation. In this tumor model, 31P nuclear magnetic resonance spectroscopic changes postradiation are temporally coincident with and may be indicative of tumor reoxygenation as measured by the tumor control dose for 50% of tumors and oxygen-sensitive microelectrodes.

Animals↗

Pregnancy outcome in survivors of advanced Hodgkin disease.

BACKGROUND: Pregnancy outcome was reported by 139 survivors of advanced Hodgkin disease treated on nine protocols of Cancer and Leukemia Group B from 1966 to 1986. METHODS: These patients provided data on 302 singleton pregnancies of a duration of at least 20 weeks that occurred before, during, or after treatment for Hodgkin disease (252, 26, and 24 pregnancies, respectively). RESULTS: There were 4 perinatal deaths, as compared with 5.7 expected. Cancer subsequently developed in 2 offspring (expected, 1.2). However, 22 newborn infants had low a birth weight, exceeding the expected number of 13.7 (relative risk 1.6; 95% confidence interval, 1.0-2.4). The excess number of low weight births occurred primarily during the period of Hodgkin disease diagnosis and treatment but is based on small numbers. CONCLUSION: No increase in adverse outcome occurred in pregnancies that antedated the development of Hodgkin disease.

Adult↗

In vivo monitoring of changes in 5-fluorouracil metabolism induced by methotrexate measured by 19F NMR spectroscopy.

We have used in vivo 19F NMR spectroscopy to study the metabolism of 5-fluorouracil (FUra) in tumors with and without pretreatment with methotrexate (MTX). Using the CD8F1 murine mammary tumor as an in vivo model, we observed signals from FUra, alpha-fluoro-beta-alanine (F beta ALA), alpha-fluoro-beta-ureidopropionic acid (FUPA), and 5-fluorouracil-nucleotides (FUN) after intravenous or intraperitoneal injection of 150 mg/kg FUra. Formation of FUN was increased about 1.7-fold in CD8F1 tumor with methotrexate pretreatment as determined by acid extraction and HPLC analysis. A comparison of in vivo NMR spectra from FUra and sequential MTX + FUra-treated tumors showed a significantly higher ratio of the FUN signal to the initial total 19F signal in the MTX + FUra-treated tumors (p less than 0.001) for animals receiving FUra either intravenously or intraperitoneally. In addition, tumors treated with MTX + FUra had significantly longer time durations during which FUN was detected, independent of the mode of administration. These experiments indicate that in vivo 19F NMR spectroscopy can be used to noninvasively monitor alterations of 5-fluorouracil metabolism that occur with administration of modulating agents such as methotrexate. Further studies, in both murine tumor models and patients, are indicated to determine if these results can be correlated with tumor response.

Animals↗

Socioeconomic status and cancer survival.

Survival data from eight Cancer and Leukemia Group B (CALGB) protocols were examined for patients with lung cancer (N = 961), multiple myeloma (N = 577), gastric cancer (N = 231), pancreatic cancer (N = 174), breast cancer (N = 87), and Hodgkin's disease (N = 58). After accounting for differences in survival rate attributable to type of cancer, initial performance status, age, and 14 other protocol-specific prognostic indicators, the additional predictive value of socioeconomic status (SES) was evaluated. Race (white v non-white) was not a significant predictor of survival time, but income and education were. People with lower annual incomes (below $5,000 per year in the years 1977 to 1981) and those with lower educational level (grade school only) showed survival times significantly shorter than those with higher income or education, respectively. These survival differences were associated with, but could not be fully explained by, severity of disease at initial presentation. SES continued to exert a small but significant impact on cancer survival, even after controlling for all known prognostic variables. Economically and educationally disadvantaged cancer patients may require treatment programs that include education about treatment and compliance, even after an initial diagnosis is made and treatment is initiated. Because SES is related to survival independent of all known prognostic variables, it should be included in the data bases of clinical trial groups to provide a more accurate test of the effectiveness of new therapies.

Adolescent↗

Changes in radiation sensitization induced by Fluosol-DA as measured by 31P nuclear magnetic resonance spectroscopy.

Numerous agents have been studied in attempts to sensitize radioresistant hypoxic tumor cells. We have investigated the effect of Fluosol-DA plus carbogen (95% oxygen and 5% CO2) on the sensitivity of a radioresistant mammary carcinoma in C3H/He mice and also on tumor metabolism by 31P nuclear magnetic resonance spectroscopy. Statistically significant increases in phosphocreatine/Pi were noted for small- (150-350 mm3) and medium- (351-650 mm3) sized tumors treated with Fluosol-DA plus carbogen. Small tumors were shown to undergo significant radiosensitization in the presence of Fluosol-DA plus carbogen and medium-sized tumors showed a lesser degree of radiosensitization. Large tumors (greater than 900 mm3) showed no effect. Fluosol-DA or carbogen alone had no effects on animals with any tumor volume, as monitored by significant changes in radiosensitivity or nuclear magnetic resonance parameters. An approximately linear relationship was found between the decrease in the values for radiation dose which yields 50% tumor control and the increase in phosphocreatine/Pi, with a correlation of r = -0.93. 31P nuclear magnetic resonance spectroscopy may be useful for monitoring changes in radiosensitivity induced by agents which alter tumor oxygenation and subsequent metabolic status.

Animals↗

Changes in the prescription patterns of psychotropic drugs for cancer patients during a 10-year period.

The use of psychotropic drugs was studied in 200 cancer patients admitted to a medical oncology unit at Memorial Sloan-Kettering Cancer Center, New York, in December 1987. When compared with a similar survey that studied prescription practices 10 years ago, there was a 30% increase in the use of psychotropic agents. Whereas prescription rates for different drug classes remained relatively stable, psychotropic drugs are now used for a greater range of reasons. The introduction of several new agents, especially short-acting benzodiazepines, has altered the physician's choices. Despite awareness of the different properties of psychotropic medications and their increased use, they are still underused, especially the antidepressants and antipsychotics when prescribed for psychologic distress.

Adult↗

Relationship of changes in pH and energy status to hypoxic cell fraction and hyperthermia sensitivity.

The relative concentrations of nucleotide triphosphates, creatine phosphate, inorganic phosphate, and pH have been evaluated as a function of tumor volume in a murine fibrosarcoma (FSaII) by 31P NMR spectroscopy. As the tumor volume increased from 60-1250 mm3, the ratio of phosphocreatine to inorganic phosphate systemically decreased. This decrease paralleled a decrease in the ratio of nucleotide triphosphate to inorganic phosphate in the same tumor volume range. The tumor pH as measured by 31P NMR decreased slightly with tumor growth. A pH of 7.17 +/- 0.07 (n = 17) was found for tumors between 60 and 150 mm3, whereas for tumors greater than 900 mm3, a pH of 7.05 +/- .03 (n = 6) was noted. Intermediate size tumors (151-900) had a pH of 7.12 +/- 0.09 (n = 18). The change in tumor energy status with tumor volume inversely paralleled the change in tumor radiobiologic hypoxic cell fraction and suggested a causal relationship between tumor nutrient status and energy status. Tumor thermal sensitivity also increased with tumor volume, suggesting a relationship between pH, energy status, and thermal sensitivity, as has been demonstrated under in vitro conditions. Each NMR parameter was found to correlate significantly with tumor volume independent of the other NMR parameters.

Adenosine Triphosphate↗