ACR Appropriateness Criteria®-Recurrent Rectal Cancer.

The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions. These Criteria are reviewed every 2 years by a multidisciplinary expert panel. The development and review of these guidelines includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.Local recurrence of rectal cancer can result in devastating symptoms for patients, including intractable pain and discharge. Prior treatment can limit subsequent treatment options. Preoperative 5-FU based chemoradiotherapy is the treatment of choice for patients with a local recurrence who did not receive adjuvant therapy after initial resection or who might have received chemotherapy alone. Chemoradiotherapy followed by evaluation for surgery is the preferred treatment for patients who have undergone previous radiotherapy after surgery. The inclusion of surgery has resulted in the best outcomes in a majority of studies. Palliative chemoradiotherapy is appropriate for patients who have received previous radiotherapy whose recurrent disease is considered inoperable. Radiotherapy can be delivered on a standard or hyperfractionated treatment schedule.Newer systemic treatments have improved response rates and given physicians more options for treating patients in this difficult situation. The use of induction chemotherapy prior to radiotherapy is an evolving treatment option. Specialized treatment modalities should be used at institutions with experience in these techniques and preferably in patients enrolled in clinical trials.

ACR Appropriateness Criteria: local excision in early-stage rectal cancer.

Low anterior resection or abdominoperineal resection is considered standard treatment for early rectal cancer. These procedures, however, carry a risk of morbidity and mortality that may not be warranted for early distal lesions, which may be treated with local excision. Emerging data has investigated the efficacy of local excision in patients with early stage rectal cancers. An expert panel designated by the American College of Radiology has reviewed supporting data, from a few prospective multi-institutional trials and a number of single-institution, retrospective reviews. The consensus recognizes the importance of accurate staging to identify patients who may be candidates for a local excision approach. Optimal candidates for local excision alone include small, low-lying T1 tumors, without adverse pathologic features. A number of procedures may be safely used including transanal, posterior trans-sphincteric, posterior proctotomy, transanal excision, or transanal microsurgery. It is important to note that none of these include lymph node evaluation, and depending on the risk of lymph node metastases, adjuvant radiation with or without chemotherapy may be warranted. Patients with positive margins or T3 lesions are at high risk of local recurrence and should be offered immediate APR or LAR. However, patients with high-risk T1 tumors, T2 tumors, or those who are not amenable to more radical surgery may benefit from adjuvant treatment. Data have also reported excellent local control rates for neoadjuvant radiation +/- chemotherapy followed by local excision in higher risk patients, but it is not yet clear if this approach reduces recurrence rates over surgery alone.

ACR Appropriateness Criteria: rectal cancer-metastatic disease at presentation.

In 2009, an estimated 40,870 new cases of rectal cancer will be diagnosed in the USA. After decades of treating metastatic colorectal cancer (CRC) with 5-fluorouracil alone, newer agents have resulted in significant improvements in disease-free and overall survival rates. These improvements stem from combinations of newer cytotoxic agents and targeted therapies. Based on performance status and burden of disease, metastatic CRC patients are generally treated with either a curative or palliative intent. Curative paradigm patients often have low burden liver or lung metastases which are technically resectable. Patients with resectable colorectal liver metastases and no evidence of any extrahepatic metastases have impressive 5-year survival rates of 30%-70% following resection. Unfortunately, only 20%-30% of patients with colorectal liver metastases are candidates for resection at initial presentation. Patients with unresectable liver or lung metastasis are candidates for local therapies including radioablation, chemoembolization, radioembolization, and stereotactic radiation therapy. In select patients with metastatic CRC, neoadjuvant or adjuvant pelvic chemoradiation (CRT) is indicated to prevent local recurrence. Patients who have resectable metastatic disease with symptomatic, obstructive, Stage T3-4 and N1, or low-lying (

ACR Appropriateness Criteria on resectable rectal cancer: expert panel on radiation oncology--rectal/anal cancer.

In what arguably may be the most pivotal recent trial in the area of resectable rectal cancer management, a randomized trial from Germany has established a regimen of preoperative chemoradiotherapy and surgery followed by additional cycles of chemotherapy alone as the standard of care for clinical stages T3 or T4, or for node-positive rectal cancer. Other clinical studies from the United States, Europe, and Asia have also influenced the treatment strategies of operable rectal cancer, as various approaches using preoperative or postoperative radiotherapy, with or without chemotherapy, have been examined. A summary of the major randomized clinical trials spanning the past several decades is provided.

ACR Appropriateness Criteria on treatment of anal cancer.

Anal cancer is a relatively rare neoplasm, accounting for roughly 4,500 cases per year. The evolution of the definitive treatment of anal cancer from a surgical to a nonsurgical approach, however, has been viewed as a model disease site in a larger paradigm shift in medicine. Organ preservation, in this case a functional anal sphincter, and durable cure are obtainable goals. To this end, anal cancer is a disease best treated primarily with chemoradiation. Although appropriate treatment can produce acceptable results, further investigation and improvement in therapy are still needed.

Prostate cancer metastatic to the external auditory canals.

A 58-year-old white man with prostate-specific antigen (PSA) level of 6 ng/mL, a Gleason score of 6 (3+3), and T2a adenocarcinoma of the prostate underwent prostatectomy. On review of the pathology, the specimen contained a Gleason score of 8 (3+5) with other high-risk features. The patient had a persistently elevated postoperative PSA level and was placed on total androgen blockade. The PSA continued to increase, and the patient developed bone-only metastatic disease. The patient was treated with palliative external-beam radiation and samarium. Six months later, he presented with bilateral hearing loss and was found to have pathologic and radiographic evidence of metastatic prostate cancer to the external auditory canals. This was an unusual late finding. The patient died shortly afterward before completing palliative treatment to the area.

Lymphovascular invasion in prostate cancer: prognostic significance in patients treated with radiotherapy after radical prostatectomy.

BACKGROUND: Lymphovascular invasion (LVI) is found in approximately 5% to 53% of specimens after radical prostatectomy (RP). Although LVI is associated with higher rates of recurrence after RP, its prognostic significance after postprostatectomy radiotherapy (P-XRT) is unclear. METHODS: The medical records of men who received P-XRT from 1991 to 2001 at 2 institutions were reviewed for the presence of LVI in RP specimens. Multiple patient variables were evaluated for their association with LVI using Fisher exact tests and Wilcoxon rank-sum tests. The time to biochemical recurrence (BCR) and the time to distant metastases (DM) after RP were analyzed using Kaplan-Meier estimations, log-rank tests, and Cox regression analyses. RESULTS: Eighteen of 160 patients (11%) who received P-XRT had LVI in their RP specimen. High Gleason score and seminal vesicle invasion were associated significantly with LVI. After a median follow-up of 8.3 years after RP, 16 patients with LVI had BCR after P-XRT, 9 of whom developed DM. The median time to BCR in patients with LVI was 2.6 years (95% confidence interval [95% CI], 1.8-5.4) compared with 7.8 years (95% CI, 6.8-10.3) in patients without LVI (P < .001). Multivariate analysis revealed an adjusted relative risk for LVI of 5.5 (P < .001). Other significant factors were Gleason score, undetectable post-RP serum prostate-specific antigen (PSA) levels, preradiotherapy serum PSA levels, and the interval from RP to P-XRT. LVI was the only significant factor associated with an increased risk of DM in univariate analysis (hazard ratio, 7.4; P < .001). CONCLUSIONS: LVI was useful as a pathologic marker for reduced efficacy of P-XRT after RP in terms of increased risk of BCR and DM. Future studies will be needed to validate these findings.

Long-term salvage radiotherapy outcome after radical prostatectomy and relapse predictors.

PURPOSE: We assessed the efficacy of salvage radiotherapy (SRT) and analyzed predictors of biochemical progression-free survival (bPFS) and distant metastasis-free survival in patients with clinically localized disease recurrence after radical prostatectomy. MATERIALS AND METHODS: The records of 114 patients treated with SRT at 2 institutions between 1991 and 2001 were retrospectively reviewed. Time to biochemical recurrence and to distant metastases was analyzed using the Kaplan-Meier estimation. Candidate predictors of bPFS and distant metastasis-free survival were analyzed using the log rank test and Cox regression. Acute and late complications were scored using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: At a median followup of 6.3 years (range 1.9 to 13.3) for SRT 4 and 6-year bPFS was 50% (95% CI 42% to 61%) and 33% (95% CI 24% to 43%), respectively. The 6-year actuarial probability of distant metastases after SRT was 14%. Multivariate analysis demonstrated an independent association of increasing Gleason score, lymphovascular invasion and lack of a complete response to SRT with decreased 5-year bDFS. These factors were associated with significantly less 5-year distant metastasis-free survival. Pre-RT prostate specific antigen greater than 2.0 ng/ml was associated with significantly decreased 5-year bDFS and distant metastasis-free survival, although it was not maintained on multivariate analysis. CONCLUSIONS: SRT results in durable prostate specific antigen control in select patients. It is well tolerated with few severe late effects. Increasing Gleason score, lymphovascular invasion and lack of a complete response to SRT are significant risks for disease progression requiring additional management.

Early ipsilateral breast tumor recurrences after breast conservation affect survival: an analysis of the National Cancer Institute randomized trial.

PURPOSE: To evaluate the effect of an ipsilateral breast tumor recurrence (IBTR) after breast-conservation therapy (BCT) on survival. METHODS AND MATERIALS: One hundred twenty-one women were randomized to BCT. Patients with an IBTR were analyzed to determine survival. Analysis was performed with Kaplan-Meier estimates, log-rank tests, and time-dependent covariate Cox models. RESULTS: At a median follow-up of 18.4 years, 27 patients had an IBTR. The median survival time after IBTR was 13.1 years. The 5-year survival rate was 91.8% (95% confidence interval [CI], 81.5-100%). The 10-year survival rate was 54.3% (95% CI, 35.8-82.6%). According to a Cox model with time-dependent covariates, the hazard ratio or relative risk of dying for those with an IBTR at <5.3 years after BCT relative to patients without an IBTR after BCT is 1.47 (95% CI, 1.02-2.12%; p = 0.04). The hazard ratio for those who relapse after 5.3 years is 0.59 (95% CI, 0.22-1.61%; p = 0.31). Age at randomization, original tumor size, and the presence of positive regional nodes at initial presentation were not found to be associated with decreased survival. CONCLUSIONS: There seems to be a significant association of early IBTR after BCT with decreased survival. Local control should be maximized.

Eighteen-year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy: the National Cancer Institute Randomized Trial.

BACKGROUND: Between 1979-1987, the National Cancer Institute conducted a randomized, prospective study of mastectomy (MT) versus breast conservation therapy (BCT) in the treatment of patients with early-stage breast carcinoma. After a median potential follow-up of 18.4 years, the authors present the updated results. METHODS: After informed consent was obtained from each patient, 237 evaluable women with clinical AJCC Stage I and Stage II breast carcinoma were enrolled on an institutionally reviewed protocol and randomly assigned to undergo modified radical MT (116 patients) or BCT (121 patients), which was comprised of lumpectomy, axillary lymph node dissection, and radiation therapy. Negative surgical margins in the lumpectomy arm were not required. The 237 randomized patients were followed for a median potential follow-up of 18.4 years. The primary endpoints were overall survival and disease-free survival. RESULTS: At a median follow-up of 18.4 years, there was no detectable difference with regard to overall survival between patients treated with MT and those treated with BCT (58% vs. 54%; P = 0.67 overall). Twenty-seven women in the BCT arm (22%) experienced an in-breast event. After censoring in-breast events in the BCT arm that were salvaged successfully by MT, disease-free survival also was found to be statistically similar (67% in the MT arm vs. 63% in the BCT arm; P = 0.64 overall). There was no statistically significant difference with regard to contralateral breast carcinoma between the two treatment arms (P = 0.70). CONCLUSIONS: After nearly 20 years of follow-up, there was no detectable difference in overall survival or disease-free survival in patients with early-stage breast carcinoma who were treated with MT compared with those treated with BCT. For BCT patients, long-term in-breast failures continued to occur throughout the duration of follow-up. There was no statistically significant difference in the incidence of contralateral breast carcinoma between the two treatment groups.

Marker seed migration in prostate localization.

PURPOSE: Marker seed location was analyzed to test the hypothesis that there is no intraseed migration within the prostate, a premise fundamental to the technique of marker seed localization of this organ. Despite increasing interest in the use of implanted seeds as fiducial markers for gland location, there are few data available with which to evaluate the validity of this technique, particularly over the entire course of external beam radiation therapy. METHODS AND MATERIALS: Between May 2001 and December 2001, after obtaining fully informed written consent, 9 patients with early stage prostate cancer were enrolled on an institutionally reviewed protocol. Patients had four to five marker seeds implanted into the prostate under transrectal ultrasound guidance before definitive radiotherapy. The porous gold seeds were each 1.2 x 2.0 mm in dimension. Seed locations from orthogonal radiographs based on the initial simulation and weekly orthogonal films were digitized using a CMS Focus planning system, thereby facilitating the determination of intraseed spacing. The digitization of the isocenter from each orthogonal pair of radiographs was used to determine digitizing error for seed localization. Pubic symphysis, bilateral femoral heads, and isocenter were also digitized and will be analyzed at a later date. RESULTS: Overall, the average migration of all the seeds in the patients was 1.2 +/- 0.2 (SD) mm. The greatest average movement of any seed in any patient was 1.9 mm over the entire 7-week course of radiotherapy. The smallest average movement was 0.6 mm. The greatest change in intraseed spacing in any of the patients during the full course of therapy was 6.6 mm. One seed in 1 patient was lost at the start of the third week of therapy and censored from analysis. Digitizing error in seed localization was calculated to be 0.20 +/- 0.03 (SD) mm. CONCLUSIONS: As an aggregate, there is negligible seed migration within the prostate over the entire course of definitive radiotherapy. However, there are small, detectable movements in individual seed locations, perhaps resulting from topographic changes in the gland secondary to seed placement, anatomic changes in bladder and rectum, or treatment itself. With respect to seed migration, prostate marker seeds represent an accurate and reliable surrogate of gland location during a full course of radiotherapy.

Phase I study of weekly gemcitabine as a radiation sensitizer for unresectable pancreatic cancer.

PURPOSE: To determine the maximal tolerated dose and dose-limiting toxicities (DLTs) of weekly gemcitabine with concurrent radiotherapy (RT) in patients with unresectable adenocarcinoma of the pancreas. METHODS AND MATERIALS: Patients who had locally advanced or recurrent unresectable pancreatic cancer were eligible. Gemcitabine was administered as a 30-min infusion once weekly for a total of five cycles during the course of RT. The starting dose of gemcitabine was 350 mg/m(2)/wk. Doses were escalated by increments of 25% in successive cohorts of 3-6 patients. RT was delivered at 180 cGy/d to a total dose of 5400-5580 cGy to the gross tumor volume. RESULTS: Nineteen patients were entered in this study through three dose levels (350-550 mg/m(2)/wk). The maximal tolerated dose was determined to be 440 mg/m(2)/wk. The DLTs were neutropenia, thrombocytopenia, and failure to receive all five cycles of gemcitabine. Other non-DLTs included 16 Grade III toxicities, which consisted of thrombosis, infection, nausea, vomiting, hypotension, constipation, diarrhea, and fatigue. One patient at each gemcitabine dose level experienced Grade IV vomiting, and the patient at the 550 mg/m(2) dose developed Grade IV anorexia. CONCLUSION: The maximal tolerated dose of gemcitabine when administered as a 30-min infusion once weekly during RT for unresectable pancreatic cancer was found to be 440 mg/m(2)/wk. The DLTs were neutropenia, thrombocytopenia, and failure to receive all five cycles of chemotherapy. Concurrent gemcitabine and RT is reasonably well tolerated and deserves additional evaluation against the current standard of care.

Low-grade follicular lymphoma of the small intestine.

BACKGROUND: Although the gastrointestinal tract is the most common site of extranodal non-Hodgkin's lymphoma (NHL), primary small intestine lymphomas remain relatively rare, especially localized low-grade follicular B-cell lymphomas. When lymphomas do occur at this site, most are high grade and require aggressive therapy. We report three cases of small intestinal follicular lymphoma diagnosed on endoscopic biopsy and review the clinical history, pathologic features, and treatment outcome. STUDY: A review of the medical records and pathology from three cases of small intestine follicular NHL was performed. The pathology specimens were formalin-fixed, paraffin-embedded tissues processed for routine microscopic examination, immunohistochemical staining, and molecular analysis. RESULTS: Histologic and immunophenotypical studies were diagnostic of grade 1 follicular lymphoma (Revised European-American Lymphoma classification/World Health Organization classification). All cases expressed bcl-2 protein, and polymerase chain reaction analysis supported the diagnosis in two cases with adequate DNA. With 23.3 months' median follow-up, one untreated and one treated patient were alive without symptoms; a third untreated patient died of a nonlymphoma cause. CONCLUSION: Isolated indolent lymphomas of the small intestine are rare. Accurate pathologic staging and histologic classification are paramount in delineating treatment options.