Tumor burden

In patients with bulky disease or a significant tumor burden, neoadjuvant chemotherapy can be used to decrease tumor burden to increase the likelihood of optimal tumor debulking during surgery.35 Typically, three cycles of the standard combination taxane/platinum regimen is administered once every 3 weeks. After surgery, the patient will receive another three to six cycles depending on response to chemotherapy. 

Like age, the WBC count at presentation is a reliable indicator of CR rate and outcome. WBC count is indicative of tumor burden, although the underlying biologic mechanisms that account for the unfavorable outcomes associated with an elevated WBC count are unclear. Patients with WBC counts of less than 50 X 103/jliL (50 x 109/L) are considered standard risk, and a higher WBC count at presentation is associated with higher risk of treatment failure (Table 92-6). 

The primary goals in the treatment of CLL are to provide palliation of symptoms and to improve overall survival. Since the current treatments for CLL are not curative, reduction in tumor burden and improvement in disease symptoms are reasonable end points, particularly in older patients. A response to therapy can be evaluated by a resolution of lymphadenopathy... 

The primary goal in the treatment of multiple myeloma is to decrease tumor burden and minimize complications associated with the disease. A watch and wait approach is an option for asymptomatic patients who have no lytic lesions in the bone. Once symptoms occur, treatment is required. Chemotherapy can be used to reduce tumor burden in patients with symptomatic disease, but increasingly, immunomodula-tors such as thalidomide and dexamethasone are initial therapy. Almost all patients will become refractory to initial treatment and will require the use of salvage therapies such as bortezomib. Autologous stem cell transplantation prolongs overall survival in patients who can tolerate high-dose chemotherapy and may be the treatment of choice for many patients. 

Oyajobi BO, Franchin G, Williams PJ, et al. Dual effects of macrophage inflammatory protein-lalpha on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease. Blood 2003 102(1) 311—319. 

Generally, a CA 15-3 cutoff of 25 U/ml is used to detect stage I breast cancer. In higher stages, the sensitivity is reported to be much better, which makes it a good test of tumor burden. CA 15-3 is reported to be elevated in other disease conditions such as liver disease (particularly chronic hepatitis, cirrhosis, and carcinoma), some inflammatory conditions (sarcoidosis, tuberculosis, systemic erythematosus), and other carcinoma (lung and ovary). For this reason, positive CA 15-3 results should be interpreted with caution (20,21). 

Generally, changes in the tumor marker concentration reflect changes in tumor burden. It has been reported that an increase in the tumor marker concentration is associated with tumor recurrences. An increase of 25 percent or more can be due to tumor progression. Similarly, a decrease could be due to tumor regression or response to therapy (18, 28, 32). 

Kavanagh KT, Hafer LJ, Kim DW, and others. 2001. Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture. J Cell Biochem 82(3) 387—398. 

Early administration of effective combination chemotherapy at a time of low tumor burden should increase the likelihood of cure and minimize emergence of drug-resistant tumor cell clones. Combination regimens have historically been more effective than single agent chemotherapy (Table 61-1). 

Monoclonal antibodies have also been proposed for detoxification of individuals suffering from drug overdose or chemical intoxication, as well as for radioimaging of tumor burden or metastatic foci. In veterinary medicine, monoclonal antibodies... 

Morris et al.66 (U.S.A.) induced Lewis lung carcinoma (LLC) in C57 black mice and subjected them to ECT constant current of 20 mA (which gave rise to 8-10 V as the voltage across the electrodes) was applied for 15 minutes. Animals treated with ECT survived longer and exhibited a small primary tumor burden at death as compared to the control group, although no complete regression of the tumor was observed. It would appear that a... 

Surgery remains the mainstay of treatment for localized disease. Approximately 30% of patients present with metastatic disease. Although nephrectomy has traditionally not been recommended in the context of metastatic disease, except in cases of pain or hemorrhage due to local tumor burden, two recent phase III studies have reported modest improvement in durations of survival when carefully selected patients undergo nephrectomy followed by interferon therapy. The larger of the two studies reported a median survival advantage of 3 months. 

Cytotoxic drugs act by first-order kinetics that is, at a given dose, they kill a constant fraction of the tumor cells rather than a fixed number of cells. For example, a drug dose that would result in a three-log cell kill (i.e., 99.9% cytotoxicity) would reduce the tumor burden of an animal that has 10 leukemic cells to 10 cells. This killing of a fraction of cells rather than an absolute number per dose is called the log cell kill hypothesis. 

The earliest detectable human cancers usually have a volume of at least 1 cc and contain 10 (1 billion) cells. This number reflects the result of at least 30 cycles of cell division, or cell doublings, and represents a kineti-cally advanced stage in the tumor s growth. Most patients actually have tumor burdens that are greater than 10 . Since the major limiting factor in chemotherapy is cytotoxicity to normal tissues, only a limited log cell kill can be expected with each individual treatment. 

There are two major factors predisposing to resistance to monoclonal antibody therapy. One is a tumor-related factor such as antigen loss, complement resistance antigen expression, intrinsic resistance, or tumor burden. Besides tumor-related factors, growing evidence has indicated that patient-related factors may account for the different responses of the patients to monoclonal antibody therapy. For example, differences in ADCC or CDC function according to individuals may increase our understanding of... 

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