Multimodality approach is the preferred treatment strategy for distal rectal cancer, including radical surgery, radiotherapy and chemotherapy. A significant proportion of patients managed by surgery, performed according to established oncological principles, appear to benefit from chemoradiation (CRT) therapy either pre- or postoperatively in terms of survival and recurrence rates.

Preoperative CRT may be associated with less acute toxicity, greater tumor response/sensitivity, and higher rates of sphincter-saving procedures when compared with postoperative course.1,2 Furthermore, tumor downstaging may lead to complete clinical response (defined as absence of residual primary tumor clinically detectable) or complete pathologic response (defined as absence of viable tumor cells after full pathologic examination of the resected specimen, pT0N0M0). These situations may be observed in 10% to 30% of patients treated by neoadjuvant CRT and may be referred as stage 0 disease.3–8 Surgical resection of the rectum may be associated with significant morbidity and mortality, and in these patients, with significant rates of stoma construction.9 Moreover, surgical resection may not lead to increased overall and disease-free survival in these patients. For this reason, it has been our policy to carefully follow these patients with complete clinical response assessed after 8 weeks of CRT completion by clinical, endoscopic, and radiologic studies without immediate surgery. Patients considered with incomplete clinical response are referred to radical surgery. Surprisingly, up to 7% of these patients may present complete pathologic response (pT0N0M0) without tumor cells during pathologic examination, despite incomplete clinical response characterized by a residual rectal ulcer.8

To determine the benefit of surgical resection in patients with stage 0 rectal cancer treated by preoperative CRT therapy, we compared long-term results of a group of patients with incomplete clinical response followed by radical surgery versus a group of patients with complete clinical response not operated on.

Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results.

Background Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance. Materials and methods The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care. Results and conclusions Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC). (ABSTRACT TRUNCATED)

Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999.

Objective. —To identify the sentinel lymph node(s) (SLN[s]) (the first node[s] draining the primary tumor in the regional lymphatic basin) in patients with invasive breast cancer and to test the hypothesis that the histologic characteristics of the SLN predict the histologic characteristics of the remaining lymph nodes in the axilla. Design. —A prospective trial. Participants. —Sixty-two patients with newly diagnosed invasive breast cancers. Intervention. —Patients underwent intraoperative lymphatic mapping using a combination of a vital blue dye and filtered technetium-labeled sulfur colloid. The SLN was identified and removed, followed by a definitive cancer operation, including a complete axillary node dissection. Main Outcome Measure. —The metastatic distribution in the axilla was determined in patients with occult nodal disease. Results. —The SLN was successfully identified in 57 (92%) of 62 patients using the 2 lymphatic mapping procedures. After localization, 18 patients (32%) were found to have metastatic disease, and the SLN tested positive in all 18 patients. There were no "skip" metastases, defined as an SLN that tested negative with higher nodes that tested positive. In 12 (67%) of 18 patients with metastatic disease, the SLN was the only site of disease. The metastatic distribution significantly favored SLN involvement. Among subjects with discordant nodal involvement, the probability of observing the distribution of SLN involvement by chance is very small (P Conclusions. —This study confirms that lymphatic mapping is technically possible in the patient with breast cancer and that the histologic characteristics of the SLN probably reflect the histologic characteristics of the rest of the axillary lymph nodes. The procedure also allows the pathologist to focus the histologic examination on 1 or 2 nodes, potentially increasing the yield of positive dissections and the accuracy of staging.

Lymphatic mapping and sentinel node biopsy in the patient with breast cancer

Productive research in patients with peritoneal carcinomatosis has moved slowly over several decades. In large part this was due to lack of standardized assessments by which cancer responses could be quantitated in a reliable and statistically evaluable manner. Recently, both laboratory and clinical assessments have been developed. Clinical research has shown that the prognosis of patients with peritoneal carcinomatosis is dependent upon preoperative and intraoperative variables [1]. These are the histologic grade of the malignancy, the preoperative tumor volume as assessed at surgery, the distribution of tumor at surgery, and the completeness of cytoreductive surgery. Also the preoperative abdominal and pelvic computed tomography (CT) scan has shown predictive value in assessment of the completeness of cytoreduction in patients with mucinous carcinomatosis [2]. The clinical research tools that are currently used in peritoneal carcinomatosis studies are reviewed in this manuscript.

Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis

During the past decade, proof of the principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been provided. The molecular basis for targeting rests on the in vitro observation that peptide receptors can be expressed in large quantities in certain tumors. The clinical impact is at the diagnostic level: in vivo receptor scintigraphy uses radiolabeled peptides for the localization of tumors and their metastases. It is also at the therapeutic level: peptide receptor radiotherapy of tumors emerges as a serious treatment option. Peptides linked to cytotoxic agents are also considered for therapeutic applications. The use of nonradiolabeled, noncytotoxic peptide analogs for long-term antiproliferative treatment of tumors appears promising for only a few tumor types, whereas the symptomatic treatment of neuroendocrine tumors by somatostatin analogs is clearly successful. The present review summarizes and critically evaluates the in vitro data on peptide and peptide receptor expression in human cancers. These data are considered to be the molecular basis for peptide receptor targeting of tumors. The paradigmatic peptide somatostatin and its receptors are extensively reviewed in the light of in vivo targeting of neuroendocrine tumors. The role of the more recently described targeting peptides vasoactive intestinal peptide, gastrin-releasing peptide, and cholecystokinin/gastrin is discussed. Other emerging and promising peptides and their respective receptors, including neurotensin, substance P, and neuropeptide Y, are introduced. This information relates to established and potential clinical applications in oncology.

/pdf/peptide-receptors-as-molecular-targets-for-cancer-diagnosis-43jzca3l3a.pdf

Peptide receptors as molecular targets for cancer diagnosis and therapy.

Forty-six patients were followed with serial CEA determinations by two CEA assays after curative resection of a primary or recurrent colonic cancer. Thirteen have had a histologically proven recurrence, of which only six (46 percent) were predicted by both assays, while seven (54 percent) were predicted by one assay only. The assays appear complementary in indicating tumor recurrence, and preliminary findings suggest that it may be beneficial to follow patients with more than one CEA assay after resection of a primary or recurrent colonic cancer.

Variation in recognition of recurrent colonic cancer by different CEA assays.

The biodistribution and kinetics of 7 monoclonal antibodies (MAb) with known reactivity against CX-I tumor were examined over 21 days using a hand-held gamma-detecting probe (Neoprobe system). Twenty-eight irnmuno-deprived (athymic) nude mice implanted with human colon adenocarcinoma CX-1 xenografts were injected intraperitoneally with 50 µCi of125I-labeled antibodies (4 mice/antibody). Of the 7 monoclonal antibodies, 4 were anti-CEA (MA, MB, MC, and MD), 2 were anti-TAG 72 (B72.3 NCI and B72.3 fermented) and one was anti-colorectal cancer (17-1A). Daily probe counts were recorded in duplicate over the tumor site and the contralateral nontumor site (background), and tumor-to-background (Tu/Bkg) ratios were calculated. Animals were sacrificed on day 21, and blood, heart, liver, spleen, lungs, kidneys, intestine, muscle, and the tumor were removed for gamma well counting. All antibodies identified the tumor as early as 24 h postinjection and speciJic tumor localization improved over time. Patterns of prolon...

An Assessment of Prolonged Reactivity of Seven Monoclonal Antibodies Against CX-1 Tumor Xenografts Using A Hand-Held Gamma-Detecting Probe

Radioimmunoguided surgery is a specific application of radioguided surgery which involves intraoperative radioimmunodetection, using a handheld radiation detection device within the operating room in a real-time fashion, for the identification of a radiolabeled antibody or antibody fragment/derivative that has been administered to a patient prior to the time of attempted intraoperative detection and for the sole purpose of guiding the successful performance of the surgical procedure. This chapter discusses (1) the history and development of radioimmunoguided surgery, (2) tumor-associated antigens, (3) monoclonal antibodies, (4) clinical applications of radioimmunoguided surgery, and (5) the future clinical relevance of radioimmunoguided surgery in cancer diagnostics and cancer therapeutics (i.e., oncologic theranostics) as a potential powerful form of antigen-directed cancer surgery.

Radioimmunoguided Surgery: Intraoperative Radioimmunodetection for the Radioguided Localization and Resection of Tumors

Radioimmunoguided brachytherapy (Rigby): a new technique for implantation of occult tumors

Validation of targeted molecular imaging using surgical specimens: A feasibility assessment using 124I-cG250 monoclonal antibody PET/CT in clear cell renal cell carcinoma

Cathy Mojzisik

Papers

Variation in recognition of recurrent colonic cancer by different CEA assays.

An Assessment of Prolonged Reactivity of Seven Monoclonal Antibodies Against CX-1 Tumor Xenografts Using A Hand-Held Gamma-Detecting Probe

Radioimmunoguided Surgery: Intraoperative Radioimmunodetection for the Radioguided Localization and Resection of Tumors

Radioimmunoguided brachytherapy (Rigby): a new technique for implantation of occult tumors

Validation of targeted molecular imaging using surgical specimens: A feasibility assessment using 124I-cG250 monoclonal antibody PET/CT in clear cell renal cell carcinoma