Measurable disease, treatment response

Cytotoxic chemotherapy is eventually required in most patients with metastatic breast cancer. Patients with hormone-receptor-negative tumors require chemotherapy as initial therapy of symptomatic metastases. Patients who respond initially to hormonal manipulations eventually cease to respond and go on to require chemotherapy. The median duration of response is 5 to 12 months, but some patients will have an excellent response to an initial course of chemotherapy and may live 5 to 10 years or longer without evidence of disease. In general, median survival of patients after treatment with commonly used drug combinations for metastatic breast cancer is 14 to 33 months. The median time to response has ranged from 2 to 3 months in most studies, but this period depends in large part on the site of measurable disease. The median time to appearance of response is between 3 and 6 weeks in patients whose disease is primarily in the skin and lymph nodes, 6 to 9 weeks in patients with metastatic lung involvement, 15 weeks in patients with hepatic involvement, and nearly 18 weeks in patients with bone involvement. Thus it is often the case that an immediate response to therapy is not... 

In Table 8.5, we compare the response rates for the two primary endpoints - disease deterioration and mortality for the Flindle et al. study. What is interesting is that for the mortality endpoint ARR shows less deviation from the null than in the case of disease deterioration, while the converse holds for the RR. This is often regarded as a major defect of the RR as a measure of treatment effect, in that it does... 

CT scan to objectively measure disease response (lung and liver metastases) -after three to four cycles of treatment,... 

Fluid biomarkers of AD currently provide indications of disease stage however, they are not robust predictors of disease progression or treatment response, and most are measured in CSF, which limits their applicability [114], Biomarkers of potential interest include CSF and peripheral levels of Ap42, protein tau, histamine, interleukins, and many other novel candidate markers in blood [7, 17, 32, 115-118],... 

Recent advances in the treatment for cancer of the colon and rectum now offer the potential to improve patient survival but for many patients, improved disease- and progression-free survival represent equally important therapeutic outcomes. Table 127-15 depicts the NCCN Practice Guidelines for chemotherapy for advanced or metastatic colorectal cancer. Although treatment approaches for metastatic colorectal cancer have been historically assessed by their ability to produce a measurable objective tumor response, which is generally believed necessary for any treatment to improve survival, the effects of therapies on survival are clinically more meaningful than their ability to induce a tumor response. However, with the availability of multiple active treatments for metastatic disease, and the likelihood that patients will receive more than one during the course of their treatment, improvements in OS with new therapies wiU be increasingly difficult to determine. 

Therapeutic approaches to NHL include radiation therapy, chemotherapy, and biologic agents. The role of radiation therapy in the treatment of NHL dEfers from its role in the treatment of Hodgkin s disease. Although the disease is responsive to radiation therapy, only a small percentage of patients with NHL present with truly localized disease that can be treated with local or regional radiation therapy. Radiation therapy is used more commonly in advanced disease, primarily as a palliative measure to control local bulky disease. 

To be useful for monitoring progression or treatment response, markers must change with disease and therapy. Key metrics of markers for monitoring therapy include responsiveness (rate of change) to disease and therapy, measurement precision, and link to clinical outcomes (surrogate validity). Complications caused by therapy must be distinguished from those associated with the disease itself. 

Treatment response to therapy is poorly measured. Measurable disease is absent after surgical excision of many tumors. 

Overall response 1. Best response recorded in measurable disease 2. NC in non-measurable lesions will reduce a CR in measurable lesions to an overall PR 3. NC in non-measurable lesions will not reduce a PR in measurable lesions 1. Best response recorded in measurable disease from treatment start to disease progression or recurrence 2. Non-PD in non-target lesion(s) will reduce a CR in target lesion(s) to an overall PR 3. Non-PD in non-target lesion(s) will not reduce a PR in target lesion(s)... 

The measurement of ER has become a standard assay in the clinical management of breast cancer. The presence of ERa identifies those breast cancer patients with a lower risk of relapse and better clinical outcome. Receptor status also provides a guideline for those tumors that may be responsive to hormonal intervention. But only about half of ER-positive patients respond to hormonal therapies. Of those who respond initially, most will eventually develop an estrogen unresponsive disease following a period of treatment even though ERa is often still present. Mutant receptors and constitutively active r eceptors as well as hormone-independent activation of the ERa are discussed. The involvement of ER 3 isoforms is under investigation. 

A cure in oncology implies that the cancer is completely gone, and the patient will have the same life expectancy as a patient without cancer. A complete response (CR) refers to complete disappearance of all cancer for 1 month after treatment. A partial response (PR) is defined as a 50% decrease in tumor diameter along with no new disease for 1 month. The term overall objective response rate refers to the combination of PR and CR. Stable disease refers to tumor that has not grown and has shrunk by less than 25% of the diameter. Disease progression refers to tumor that has spread or the primary tumor has increased in size by 25%. Some cancers, such as leukemia, cannot be measured by size, so biopsy of the bone marrow provides a cellular indication of absence or presence of disease. 

Patients must be monitored to assess their response to treatment and to detect recurrent diseases. PSA as a specific marker for prostate cancer is most useful in monitoring patients who have been treated with radical prostatectomy, radiation therapy, or endocrine therapy. The concentration of PSA falls to undetectable levels following a radical prostatectomy because all prostate tissue has been removed. Generally, PSA is measured at periodic intervals. In studies, the extent of disease at the time of surgery correlated well with the postoperative PSA concentration. A significant measurable PSA concentration after prostatectomy indicates that residual tumor may be present. PSA concentrations decline gradually after radiation therapy (36). 

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