Residual disease

In most instances, external-beam radiation therapy used in conjunction with breast-conserving procedures involves 4 to 6 weeks of radiation therapy directed to the breast tissue to eradicate residual disease. Complications associated with radiation therapy to the breast are minor and include reddening and erythema of the breast tissue and subsequent shrinkage of total breast mass beyond that predicted on the basis of breast tissue removal. Some clinical situations also require postmastectomy radiation therapy as well (see section on locally advanced breast cancer). 

The histology of the disease is a prognostic factor. For instance, clear-cell and undifferentiated tumors do not respond as well to chemotherapy.2 The extent of residual disease and tumor grade are also predictive of response to chemotherapy and overall survival.2 There are other prognostic factors that may predict how well a patient will respond to adjuvant chemotherapy. 

Ultrasensitive assays for PSA contribute to the earlier detection of prostate cancer relapse and (or) residual disease in prostatectomized patients as well as the more timely evaluation of response to current therapies. PSA determinations can be useful in detecting metastatic or persistent disease in patients following surgical or medical treatment of prostate cancer. Persistent elevation of PSA following treatment, or an increase in the pretreatment PSA concentrations, is indicative of recurrent or residual disease. Hence, PSA is widely accepted as an aid in the management of prostate cancer patients, and serum levels are most useful when sequential values are obtained and monitored over time. After complete removal of the prostate gland (radical prostatectomy), PSA levels should become very low or undetectable. A rise of the serum PSA level in prostatectomy patients indicates residual prostate tissue, recurrence, or metastasis of the disease (13, 16, 24, 36). 

RT is administered to the entire breast over 4 to 6 weeks to eradicate residual disease after BCT. Reddening and erythema of the breast tissue with subsequent shrinkage of total breast mass are minor complications associated with RT. 

The combination of tyrphostins with cytotoxic drugs can be followed by immunotherapy in order to eliminate residual disease. Though such combinations have not yet been examined, the combination of AG 490 and IL-12 against IL-6 dependent multiple myeloma recently showed impressive tumor suppressive effects [54], suggesting that the general idea may indeed be correct. 

Molecular weight markers for electrophoresis and hybridization techniques are widely used. These markers provide information in regard to molecular weights of rearranged bands. These techniques are useful in monitoring patients for relapse or residual disease status. The 32P-labeled and biotinylated DNA molecular weight markers provide visualization on the film and membrane. Hardware systems with band size computation capabilities are available. 

Tl. Thompson, J. D., Brodsky, I., and Yunis, J. J., Molecular quantification of residual disease in chronic myelogenous leukemia after bone marrow transplantation. Blood 79, 1629-1635 (1992). 

An important demonstration of the efficacy of a MAb in minimal residual disease was achieved usiug MAb 17-lA (directed against the EGP-2 or EpCAM antigen as described previously) in patients with stage III colorectal cancer. Following surgical resection, MAb therapy reduced the overall death rate by 32% and the rate of recurrence by 23% [122]. 

In addition, combination therapy trials of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in refractory and newly diagnosed patients suggests that rituximab may also have a role in the eradication of residual disease. This combination appears to be a viable treatment option for relapsed low-grade non-Hodgkin lymphoma... 

Encouraging results with MAb-drug conjugates were seen in a phase I study with a conjugate of calicheamicin yli and a humanized anti-CD33 MAb in patients with refractory or relapsed AML [131]. Results support further evaluation in a setting of newly diagnosed or minimal-residual disease. 

Roth (47) 60 Mixed III (N2 not required some IIIB) CyEP x 3 preop. and x 3 postop. Only if residual disease at surgery 56% 15% <.05... 

Patients with locally advanced colon cancer and suspected microscopic or gross residual disease after surgery pose a difficult management problem. Postoperative radiation therapy in addition to standard chemotherapy may have some utility in sterilizing residual disease. In retrospective studies, local radiation therapy with or without concurrent chemotherapy achieves local control in46-70% of patients with microscopic residual... 

Selection of patients based on pathology Identify high-risk areas or residual disease... 

Minimal Residual Disease, Viral Load, and Gene Quantitation. 221... 

Adjuvant drug treatment is given after local therapy to patients who do not show evidence of macroscopic residual disease, but who are judged to be at high risk of having microscopic metastases and therefore risk of relapse, as indicated by adverse tumor characteristics. Experimental evidence based on... 

Zinzani et at. showed in a study of 75 patients with malignant lymphomas that [ F]-FDG-PET positivity after induction of treatment is highly predictive for the presence of residual disease, with significant differences in terms of recurrence free survival (9% vs. 91%). Conventional imaging methods such as CT and MRI cannot differentiate reliably between scar tissue and vital tumor tissue. Therefore, [ F]-FDG-PET was recently introduced into clinical routine for therapy control and evaluation of early treatment response [91]. 

With relevance to the administration of thiopurines in the early course of childhood ALL, the BFM Study Group reported on the association of TPMT genotype and minimal residual disease (MRD) in 810 children with childhood ALL enrolled into their trial ALL-BFM 2000 (206). In this trial, DNA-based MRD analysis after induction and after consolidation treatment was used for risk-adapted treatment stratification. A 4-week cycle of 6-MP was applied in-between these two MRD measurements. In patients homozygous for the TPMT 1 allele or those heterozygous for a variant TPMT allele, MRD levels on treatment day 33 were equally distributed between the groups. However, when MRD levels were assessed on treatment day 78, after administration of consolidation... 

Brisco MJ, Condon J, Hughes E et al. Outcome predietion in childhood acute lymphoblastic leukaemia by molecular quantification of residual disease at the end of induction. Lancet 1994 343 196-200. 

Cave H, van der Werff ten Bosch J, Suciu S et al. European Organization for Research and Treatment of Cancer-Childhood Leukemia Cooperative Group. Clinical significance of minimal residual disease in childhood acute lymphoblastie leukemia. N Engl J Med 1998 339 591-598. 

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