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.

Tumor-associated glycoprotein-72 (TAG-72) is a mucin-like high-molecular-weight glycosylated protein complex overexpressed by many adenocarcinomas. Antigen-directed cancer surgery using radiolabeled anti-TAG-72 murine monoclonal antibodies (muMAbs) has been previously investigated for colorectal cancer. Survival analysis of primary colorectal cancer patients with a minimum of 15-year follow-up after antigen-directed cancer surgery was performed to assess the impact of complete surgical resection of all detectable radiolabeled anti-TAG-72 muMAb. Survival analysis was performed on 92 patients (study group) with primary colorectal cancer (July 1990 to August 1995) treated with antigen-directed cancer surgery using 125I-labeled anti-TAG-72 muMAb. The study group was subdivided into those with no detectable TAG-72 antigen-bearing tissues (TAG-72 negative, N = 33) and those with persistent detectable TAG-72 antigen-bearing tissues (TAG-72 positive, N = 59) at completion of surgery. Comparisons were made with a control group (546 patients) from the same time period. Study group and control group were demographically similar, as were TAG-72-negative subgroup and TAG-72-positive subgroup. TAG-72-negative subgroup had significantly improved median survival (8.8 versus 2.5 years; P = 0.005) and time-dependent survival (45.4% versus 22.0% at 10 years; P = 0.002 and 39.4% versus 20.3% at 15 years; P = 0.003) compared with TAG-72-positive subgroup. TAG-72 positivity was as an independent predictor of long-term mortality risk, when controlled for pathologic stage of disease. Absence of detectable TAG-72 antigen within the surgical field at completion of antigen-directed cancer surgery for primary colorectal cancer is of significant prognostic value, conferring a long-term survival advantage to those in whom complete surgical removal of all tissues with detectable radiolabeled anti-TAG-72 muMAb was accomplished.

Antigen-Directed Cancer Surgery for Primary Colorectal Cancer: 15-Year Survival Analysis

Tumors marked with a radiolabeled antibody may be located by two different techniques. The first is the diagnostic use of a gamma camera to produce an image. The second is the clinical use of a gamma-sensitive probe to ‘home in’ on tumors intraoperatively. Since the two techniques are quite different, it is not surprising that they differ in advantages, limitations, and design.

Radioimmunoguided surgery: a new intraoperative approach to the detection of tumor.

Clear cell renal cell carcinoma (ccRCC) presents problems for urologists in diagnosis, treatment selection, intraoperative surgical margin analysis, and long term monitoring. In this paper we describe the development of a radiolabeled antibody specific to ccRCC (124I-cG250) and its potential to help urologists manage each of these problems. We believe 124I-cG250, in conjunction with perioperative Positron emission tomography/computed tomography imaging and intraoperative handheld gamma probe use, has the potential to diagnose ccRCC, aid in determining a proper course of treatment (operative or otherwise), confirm complete resection of malignant tissue in real time, and monitor patients post-operatively.

https://journals.sagepub.com/doi/pdf/10.1177/1756287209105264

PET/CT imaging of clear cell renal cell carcinoma with 124I labeled chimeric antibody:

BACKGROUND: 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) scanning is a widely accepted preoperative tumor imaging modality. Herein, we evaluate the becquerel (Bq) as a potential novel quantitative PET measure for application of surgical specimen imaging. METHODS: Retrospectively, PET-avid lesions that could be followed from preoperative imaging, confidently identified in the operating room, imaged ex vivo, and correlated with histopathology were included in this study. Bq counts from both in vivo (preoperative) and ex vivo (surgical specimen) PET/CT images were measured and correlated with histopathology. RESULTS: Fifty-five PET-avid lesions in 37 patients were included. Forty-six of 55 PET-avid lesions identified were found to contain malignancy on histopathology. Mean Bq counts for the PET-avid lesions were significantly higher that the adjacent PET-nonavid areas (background) within both in vivo and ex vivo imaging (P < .001 and P < .001, respectively). When analyzing all 55 lesions, we found significant increases in Bq levels. PET-avid lesions from in vivo to ex vivo images (P < .001) without significant increases in Bq levels in PET-nonavid lesions from in vivo to ex vivo images (P = .06). When comparing Bq levels between the 2 groups (malignant and benign), we found significantly higher Bq counts in the malignant group on in vivo imaging (P = .02) as well as significantly lower Bq counts in FDG-nonavid areas on ex vivo imaging (P = .04) within the malignant group. Significant differences in PET-avid to PET-nonavid Becquerels ratios within both in vivo and ex vivo images (P = .004, P = .002 respectively) were found, with ex vivo ratio being significantly higher (P < .001). CONCLUSIONS: 18 F-FDG PET/CT imaging using Bqs is the potential to discern malignant lesions from benign tissues within both in vivo and ex vivo scans.

Perioperative 18F-fluorodeoxyglucose–guided imaging using the becquerel as a quantitative measure for optimizing surgical resection in patients with advanced malignancy

Cathy Mojzisik

Papers

Antigen-Directed Cancer Surgery for Primary Colorectal Cancer: 15-Year Survival Analysis

Radioimmunoguided surgery: a new intraoperative approach to the detection of tumor.

PET/CT imaging of clear cell renal cell carcinoma with 124I labeled chimeric antibody:

Perioperative 18F-fluorodeoxyglucose–guided imaging using the becquerel as a quantitative measure for optimizing surgical resection in patients with advanced malignancy

Preferential Localization of Antibody Combinations in Tumor Xenografts in Nude Mice1