Presacral Nodes Research Articles

Cancer‐specific survival after radical cystectomy and standardized extended lymphadenectomy for node‐positive bladder cancer: prediction by lymph node positivity and density

To investigate the associations between different overall or topographically restricted lymph node (LN) variables and cancer-specific survival (CSS) after radical cystectomy (RC) and extended LN dissection (LND) with curative intent in patients with LN-positive bladder cancer. Between 2001 and 2006, 152 patients had RC with standardized extended LND for bladder cancer with curative intent. Patients with positive LNs were stratified according to the median of the LN variables (LNs removed, number of positive LNs, LN density). CSS was related to overall and topographically restricted LN variables, e.g. different levels of LND, and relationships were tested by univariate and multivariate analyses. Level 1 LND comprised the regions of the external and internal iliac LNs and of the obturator LNs, level 2 the templates of common iliac and presacral LNs, and level 3 the para-aortic and paracaval LNs up to the inferior mesenteric artery. The mean (range) follow-up was 22 (1-84) months. LN metastases were diagnosed in 46 of the 152 patients (30%) with extended LND. In these 46 patients, the median number of removed LNs was 33 (level 1, 15.5; level 2, 9.0; level 3, 7.0), the median number of positive LNs was 3 (1.5, 0.5 and 0.0, respectively) and the median LN density was 0.11 (0.10, 0.02 and 0.0, respectively). The CSS was 76% at 1 year and 23% at 3 years. There were significant correlations between the 3-year CSS and the overall LN density (< or =0.11 vs >0.11; 34% vs 8%, P = 0.008), and the total number of positive LNs (< or =3 vs >3; 33% vs 8%; P = 0.05). Overall LN density (hazard ratio 0.33, 95% confidence interval 0.15-0.72; P = 0.006) was an independent predictor for CSS in multivariate analysis. CONCLUSIONS Overall LN density is an independent predictor of survival after RC and extended LND with curative intent. Evaluation of topographically restricted LN positivity and density for different regions and levels of LND does not improve the prediction of CSS compared with overall LN positivity and density. A low incidence of level 3 LN positivity questions the clinical relevance of removing para-aortic and paracaval LNs. However, our data need to be confirmed by a prospective randomized trial.

The Role and Extent of Pelvic Lymphadenectomy in the Management of Patients with Invasive Urothelial Carcinoma

Lymph node metastases are the most important prognostic variable in determining outcome following radical cystectomy. An anatomic bilateral node dissection includes at a minimum the external and internal iliac and obturator lymph nodes. An extended node dissection may include the distal aortic and vena caval nodes, bilateral common iliac, and pre-sacral nodes, which receive direct lymphatic drainage from the posterior bladder and trigone. This approach sets up the cystectomy, maximizes sensitivity for detection of nodal metastasis, assures optimum local pelvic cancer control, and accurately identifies those high-risk patients with node metastases who may benefit from adjuvant chemotherapy. Lymph node retrieval is affected by several variables of node specimens addition to the anatomic extent of the node dissection. These include presentation to the pathologist in packets, specimen processing and what the pathologist calls a lymph node, and patient age. The current TNM staging system accounts for the number and size of node metastases and may be improved by incorporating lymph node density, which is a composite variable incorporating the number of positive nodes and number of nodes retrieved--a possible surrogate for the extent of the node dissection. Innovations in imaging including novel MRI contrast agents and lymphoscintigraphy may improve the pre-treatment and intra-operative identification of node metastases and lymphatic anatomy. Minimally invasive surgical techniques including robotic-assisted laparoscopic cystectomy may improve peri-operative outcomes but must meet the standard of anatomic node dissection and long-term cancer control afforded by the gold standard of anatomic radical cystectomy and bilateral pelvic and iliac node dissection.

Extended lymph node dissection in patients with urothelial cell carcinoma of the bladder: can it make a difference?

We compared extended and limited lymph node dissections performed during radical cystectomy with regard to impact on survival and time to recurrence in bladder cancer patients. We analyzed 170 patients who underwent radical cystectomy for urothelial carcinoma between January 1997 and December 2005. From 1997 to 2000, 69 of the patients were subjected to limited lymph dissection that included perivesical nodes and nodes in the obturator fossa. In 2001-2005, the remaining 101 patients underwent extended lymph dissection that included perivesical nodes; nodes in the obturator fossa; the internal, external, and common iliac nodes; and the presacral nodes. Tumors penetrating the bladder wall (pT3 and pT4a) were more common in the extended than in the limited dissection group (48 and 33%, respectively). The median numbers of lymph nodes removed in the two groups were 37 and 8, respectively. Lymph node metastases were detected in 38% of the extended dissection patients but only in 17% of the limited dissection patients. There was no significant difference in survival or time to recurrence between the two groups. Subgroup analyses showed a significantly longer time to recurrence (HR 0.45, 95% CI 0.22-0.93; P = 0.032) in patients with non-organ-confined disease who underwent extended lymph node dissection. In a multivariate analysis adjusting for tumor stage, lymph node status, age, sex, and adjuvant chemotherapy, there was a significantly improved survival (HR 0.47, 95% CI 0.25-0.88; P = 0.018) and time to recurrence (HR 0.42, 95% CI 0.23-0.79; P = 0.007) in the patients with extended lymph node dissections. Extended lymph node dissection did not improve disease-specific survival, but was in multivariate analysis related to significantly improved disease-specific survival and prolonged time to recurrence in radical cystectomy patients. These results should be interpreted cautiously, since they might have been affected by stage migration and the shorter follow-up in the extended dissection group.

RTOG GU Radiation Oncology Specialists Reach Consensus on Pelvic Lymph Node Volumes for High-Risk Prostate Cancer

Radiation therapy to the pelvic lymph nodes in high-risk prostate cancer is required on several Radiation Therapy Oncology Group (RTOG) clinical trials. Based on a prior lymph node contouring project, we have shown significant disagreement in the definition of pelvic lymph node volumes among genitourinary radiation oncology specialists involved in developing and executing current RTOG trials. A consensus meeting was held on October 3, 2007, to reach agreement on pelvic lymph node volumes. Data were presented to address the lymph node drainage of the prostate. Extensive discussion ensued to develop clinical target volume (CTV) pelvic lymph node consensus. Consensus was obtained resulting in computed tomography image-based pelvic lymph node CTVs. Based on this consensus, the pelvic lymph node volumes to be irradiated include: distal common iliac, presacral lymph nodes (S(1)-S(3)), external iliac lymph nodes, internal iliac lymph nodes, and obturator lymph nodes. Lymph node CTVs include the vessels (artery and vein) and a 7-mm radial margin being careful to "carve out" bowel, bladder, bone, and muscle. Volumes begin at the L5/S1 interspace and end at the superior aspect of the pubic bone. Consensus on dose-volume histogram constraints for OARs was also attained. Consensus on pelvic lymph node CTVs for radiation therapy to address high-risk prostate cancer was attained and is available as web-based computed tomography images as well as a descriptive format through the RTOG. This will allow for uniformity in evaluating the benefit and risk of such treatment.

Variation in the Definition of Clinical Target Volumes for Pelvic Nodal Conformal Radiation Therapy for Prostate Cancer

We conducted a comparative study of clinical target volume (CTV) definition of pelvic lymph nodes by multiple genitourinary (GU) radiation oncologists looking at the levels of discrepancies amongst this group. Pelvic computed tomography (CT) scans from 2 men were distributed to 14 Radiation Therapy Oncology Group GU radiation oncologists with instructions to define CTVs for the iliac and presacral lymph nodes. The CT data with contours were then returned for analysis. In addition, a questionnaire was completed that described the physicians' method for target volume definition. Significant variation in the definition of the iliac and presacral CTVs was seen among the physicians. The minimum, maximum, mean (SD) iliac volumes (mL) were 81.8, 876.6, 337.6 +/- 203 for case 1 and 60.3, 627.7, 251.8 +/- 159.3 for case 2. The volume of 100% agreement was 30.6 and 17.4 for case 1 and 2 and the volume of the union of all contours was 1,012.0 and 807.4 for case 1 and 2, respectively. The overall agreement was judged to be moderate in both cases (kappa = 0.53 (p < 0.0001) and kappa = 0.48 (p < 0.0001). There was no volume of 100% agreement for either of the two presacral volumes. These variations were confirmed in the responses to the associated questionnaire. Significant disagreement exists in the definition of the CTV for pelvic nodal radiation therapy among GU radiation oncology specialists. A consensus needs to be developed so as to accurately assess the merit and safety of such treatment.

Dosimetric Comparison of Bone Marrow-Sparing Intensity-Modulated Radiotherapy Versus Conventional Techniques for Treatment of Cervical Cancer

To compare bone marrow-sparing intensity-modulated pelvic radiotherapy (BMS-IMRT) with conventional (four-field box and anteroposterior-posteroanterior [AP-PA]) techniques in the treatment of cervical cancer. The data from 7 cervical cancer patients treated with concurrent chemotherapy and IMRT without BMS were analyzed and compared with data using four-field box and AP-PA techniques. All plans were normalized to cover the planning target volume with the 99% isodose line. The clinical target volume consisted of the pelvic and presacral lymph nodes, uterus and cervix, upper vagina, and parametrial tissue. Normal tissues included bowel, bladder, and pelvic bone marrow (PBM), which comprised the lumbosacral spine and ilium and the ischium, pubis, and proximal femora (lower pelvis bone marrow). Dose-volume histograms for the planning target volume and normal tissues were compared for BMS-IMRT vs. four-field box and AP-PA plans. BMS-IMRT was superior to the four-field box technique in reducing the dose to the PBM, small bowel, rectum, and bladder. Compared with AP-PA plans, BMS-IMRT reduced the PBM volume receiving a dose >16.4 Gy. BMS-IMRT reduced the volume of ilium, lower pelvis bone marrow, and bowel receiving a dose >27.7, >18.7, and >21.1 Gy, respectively, but increased dose below these thresholds compared with the AP-PA plans. BMS-IMRT reduced the volume of lumbosacral spine bone marrow, rectum, small bowel, and bladder at all dose levels in all 7 patients. BMS-IMRT reduced irradiation of PBM compared with the four-field box technique. Compared with the AP-PA technique, BMS-IMRT reduced lumbosacral spine bone marrow irradiation and reduced the volume of PBM irradiated to high doses. Therefore BMS-IMRT might reduce acute hematologic toxicity compared with conventional techniques.

Protocol for the Examination of Specimens From Patients With Primary Carcinomas of the Colon and Rectum

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the “Surgical Pathology Cancer Case Summary (Checklist)” portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of this document.

SU-GG-T-71: Dosimetric Comparison of Bone Marrow-Sparing Intensity Modulated Radiation Theraphy Versus Conventional Techniques for the Treatment of Cervical Cancer

Purpose: To compare bone marrow‐sparing intensity modulated pelvic radiation therapy (BMS‐IMRT) to conventional (AP/PA and 4‐field box) techniques in the treatment of cervical cancer.Method and Materials: Seven cervical cancer patients treated with concurrent chemotherapy and IMRT were analyzed. We compared BMS‐IMRT to AP/PA and 4‐field box plans. All plans were normalized to cover PTV with the 99% isodose line. The clinical target volume (CTV) consisted of the pelvic and presacral lymph nodes, uterus and cervix, upper vagina, and parametrial tissue. A 1.0 cm uniform margin was added to create the PTV. Normal tissues included bowel, bladder, and pelvic bone marrow (PBM), which comprised the lumbosacral spine (LSBM), ilium (IBM), and ischium, pubis, and proximal femora (lower pelvis bone marrow — LPBM). Dose volume histograms for PTV and normal tissues were compared for BMS‐IMRT vs. 4‐field box and AP/PA plans. Results: BMS‐IMRT was superior to 4‐field box in reducing the dose to PBM, small bowel, rectum and bladder. Compared to AP/PA, BMS‐IMRT reduced the PBM volume receiving a dose above 16.4 Gy, however, that receiving below this threshold dose was increased. BMS‐IMRT reduced IBM, LPBM and bowel radiation above 27.7 Gy, 18.7 Gy, and 21.1 Gy, respectively, but increased dose below these thresholds, compared to AP/PA plans. BMS‐IMRT reduced the volume of LSBM, rectum, small bowel, and bladder at all dose levels in all 7 patients. Conclusion: BMS‐IMRT reduced irradiation of PBM compared to 4‐field box techniques. Compared to AP/PA, BMS‐IMRT reduced LSBM irradiation and reduced the volume of PBM irradiated to high doses, but increased that irradiated to low doses. BMS‐IMRT may reduce acute HT compared to conventional techniques.

Outcome After Radical Cystectomy With Limited or Extended Pelvic Lymph Node Dissection

We compared recurrence patterns and survival of patients with urothelial bladder cancer undergoing radical cystectomy who either had limited or extended pelvic lymph node dissection at 2 institutions between 1987 and 2000. Two consecutive series of patients treated with radical cystectomy and limited pelvic lymph node dissection (336; Cleveland Clinic) and extended pelvic lymph node dissection (322; University of Bern) were analyzed. All cases were staged N0M0 prior to radical cystectomy, and none were treated with neoadjuvant radiotherapy or chemotherapy. Patients with PTis/pT1 and pT4 disease were excluded from analysis. Pathological characteristics based on the 1997 TNM system and recurrence patterns were determined. The overall lymph node positive rate was 13% for patients with limited and 26% for those who had extended pelvic lymph node dissection. The 5-year recurrence-free survival of patients with lymph node positive disease was 7% for limited and 35% for extended pelvic lymph node dissection. The 5-year recurrence-free survival for pT2pN0 cases was 67% for limited and 77% for extended pelvic lymph node dissection, and the respective percentages for pT3pN0 cases were 23% and 57% (p <0.0001). The 5-year recurrence-free survival for pT2pN0-2 cases was 63% for limited and 71% for extended pelvic lymph node dissection, and for pT3pN0-2 cases the respective figures were 19% and 49% (p <0.0001). Incidence of local and systemic failure correlated closely with pathological stage for both series. Our data suggest that limited pelvic lymph node dissection is associated with suboptimal staging, poorer outcome for patients with node positive and node negative disease, and a higher rate of local progression. Extended pelvic lymph node dissection allows for more accurate staging and improved survival of patients with nonorgan confined and lymph node positive disease.

Where to look for the sentinel lymph node in cervical cancer

The aim of this study was to analyze lymphatic spread to pelvic, parametrial, and paraaortic lymph nodes in patients with cervical cancer. We reviewed 619 patients with invasive cervical cancer treated by radical abdominal hysterectomy and systematic pelvic or pelvic and paraaortic lymphadenectomy between 1971 and 2005. The present study included 61 patients with one positive lymph node (10%) and 59 patients with two positive lymph nodes (10%) at any location. The external iliac (43%) and obturator (26%) regions and the parametrium (21%) were the most commonly involved pelvic lymph node sites with solitary metastases. Isolated metastases to common iliac, presacral (internal iliac), and paraaortic nodes were found in 7%, 1%, and 1% of patients, respectively. Patients with 2 positive nodes had 1 parametrial and 1 pelvic node involved (32%), 2 ipsilateral positive nodes (31%), 1 positive lymph node on both sides of the pelvis (27%), and 2 positive nodes within the parametrium (10%). In cervical cancer patients with only 1 positive lymph node, this node is most frequently located within the external iliac and obturator regions and the parametrium. Sentinel node identification should primarily address these lymph node sites. If 1 positive lymph node is found, further metastases are unpredictable within pelvic and parametrial lymph node sites. Paraaortic spread without pelvic node involvement is rare.

Optimal organ-sparing intensity-modulated radiation therapy (IMRT) regimen for the treatment of locally advanced anal canal carcinoma: a comparison of conventional and IMRT plans

BackgroundTo compare the dosimetric advantage of three different intensity-modulated radiation therapy (IMRT) plans to a three dimensional (3D) conventional radiation treatment for anal cancer with regards to organs-at-risk (OAR) avoidance, including iliac bone marrow.MethodsFive patients with T1-3 N0-1 anal cancer and five with T4 and/or N2-3 tumors were selected. Clinical tumor volume (CTV) included tumor, anal canal and inguinal, peri-rectal, and internal/external iliac nodes (plus pre-sacral nodes for T4/N2-3 tumors). Four plans were generated: (A) AP/PA with 3D conformal boost, (B) pelvic IMRT with conformal boost (C) pelvic IMRT with IMRT boost and (D) IMRT with simultaneous integrated boost (SIB). The dose for plans (A) to (C) was 45 Gy/25 followed by a 14.4 Gy/8 boost, and the total dose for plan (D) (SIB) was 59.4 Gy/33. Coverage of both PTV and the volume of OAR (small bowel, genitalia, iliac crest and femoral heads) receiving more than 10, 20, 30, and 40 Gy (V10, V20, V30, V40) were compared using non parametric statistics.ResultsCompared to plan (A), IMRT plans (B) to (D) significantly reduced the V30 and V40 of small bowel, bladder and genitalia for all patients. The V10 and V20 of iliac crests were similar for the N0-1 group but were significantly reduced with IMRT for the N2-3/T4 group (V20 for A = 50.2% compared to B = 33%, C = 32.8%, D = 34.3%). There was no statistical difference between 2-phase (arm C) and single-phase (SIB, arm D) IMRT plans.ConclusionIMRT is superior to 3D conformal radiation treatment for anal carcinoma with respect to OAR sparing, including bone marrow sparing.

Consensus Guidelines for Delineation of Clinical Target Volume for Intensity-Modulated Pelvic Radiotherapy in Postoperative Treatment of Endometrial and Cervical Cancer

To develop an atlas of the clinical target volume (CTV) definitions for postoperative radiotherapy of endometrial and cervical cancer to be used for planning pelvic intensity-modulated radiotherapy. The Radiation Therapy Oncology Group led an international collaboration of cooperative groups in the development of the atlas. The groups included the Radiation Therapy Oncology Group, Gynecologic Oncology Group, National Cancer Institute of Canada, European Society of Therapeutic Radiology and Oncology, and American College of Radiology Imaging Network. The members of the group were asked by questionnaire to define the areas that were to be included in the CTV and to outline theses areas on individual computed tomography images. The initial formulation of the group began in late 2004 and culminated with a formal consensus conference in June 2005. The committee achieved a consensus CTV definition for postoperative therapy for endometrial and cervical cancer. The CTV should include the common, external, and internal iliac lymph node regions. The upper 3.0 cm of the vagina and paravaginal soft tissue lateral to the vagina should also be included. For patients with cervical cancer, or endometrial cancer with cervical stromal invasion, it is also recommended that the CTV include the presacral lymph node region. This report serves as an international template for the definition of the CTV for postoperative intensity-modulated radiotherapy for endometrial and cervical cancer.

Radical Cystectomy and Extended Pelvic Lymphadenectomy: Survival of Patients With Lymph Node Metastasis Above the Bifurcation of the Common Iliac Vessels Treated With Surgery Only

We assessed the clinical outcome in patients with invasive bladder cancer and lymph node metastasis above the bifurcation of the common iliac vessels treated with radical cystectomy including extended pelvic lymph node dissection without adjunct therapy. Between 1993 and June 2005 a total of 336 consecutive patients underwent radical cystectomy and extended pelvic lymphadenectomy without preoperative or postoperative chemotherapy by 1 surgeon. A total of 263 patients (78.3%) had orthotopic bladder reconstruction. The pelvic lymph node dissection began at the distal aorta including the common and external iliac lymph nodes, and the periaortic, presacral and obturator fossa nodes. The lymphatic tissue removed above and below the bifurcation of the common iliac vessels was submitted separately for histopathological analysis. Data were prospectively entered into a database that forms the basis of this cohort study. The 5-year overall and recurrence-free survival rates in the entire study population of 336 patients were 68% and 69%, respectively. Overall 64 patients (19%) had lymph node metastases of whom 22 (34.4%) had lymph node involvement above the bifurcation of the common iliac vessels outside the template of the standard lymph node dissection. The median number of retrieved lymph nodes was 27 (range 7 to 78) and in those with lymph node metastases 27 (range 11 to 49) included 8 (range 0 to 17) above the bifurcation and 18 (range 8 to 41) below the bifurcation of the common iliac vessels in the true pelvis. Lymph node involvement proved a significant adverse prognostic factor with a 5-year probability of survival of 39% vs 76%. The overall 5-year survival rates was similar in patients with lymph node involvement above the bifurcation of the common iliac vessels (37%) compared to the entire population with lymph node metastasis (41%) and to those with lymphatic metastases in the true pelvis below the bifurcation of the common iliac vessels (42%). The survival rate was significantly higher in patients with 5 or less involved lymph nodes (50% vs 13%, p <0.002) and in those with a lymph node density (number of lymph nodes involved/total number of lymph nodes removed) less than 20% (25% vs 47%, p <0.05), but it did not relate to the total number of retrieved lymph nodes. Overall 34% of our patients with lymph node metastases had nodal involvement in the common iliac, periaortic and presacral regions after radical cystectomy for bladder cancer. Survival was similar in this group of patients with lymphatic metastasis outside the boundaries of the standard pelvic lymph node dissection template compared to the entire population with lymph node metastasis. This finding underscores the contention that extended dissection not only provides the most accurate staging but also offers the patient the best chance of survival. Following radical cystectomy patients can be stratified into risk groups according to tumor stage, lymph node involvement, number of metastatic nodes and lymph node density. Our results support the idea that the benchmark for radical cystectomy should include extensive pelvic lymph node dissection with anatomical boundaries including the common iliac and presacral nodes.

Pattern of lymph node metastasis and the optimal extent of pelvic lymphadenectomy in FIGO stage IB cervical cancer

To evaluate the distribution pattern of lymph node metastasis and to determine the optimal extent of pelvic lymphadenectomy (LA) in FIGO stage IB cervical cancer. The medical records of 187 patients with FIGO stage IB cervical cancer from March 1996 to December 2002 were reviewed retrospectively. The distribution pattern and risk factors of lymph node metastases were analyzed in 31 patients with lymph node metastases confirmed surgically. One hundred patients, who underwent type III hysterectomy with pelvic LA but did not receive any adjuvant treatment, were analyzed to evaluate whether the extent of LA affected the prognosis of FIGO stage IB cervical cancer. Type I LA included the external iliac nodes, hypogastric nodes, obturator nodes, and parametrial nodes. Type II LA included the pelvic nodes described in type I LA, the common iliac nodes, gluteal nodes, deep inguinal nodes and sometimes the presacral nodes. Solitary lymph node metastasis confined to one node group was seen in the obturator, external iliac or hypogastric lymph nodes. All patients with lymph node metastases at multiple sites had metastasis in at least one of these lymph-node groups. There was no significant difference in disease-free survival and overall survival in patients without pathologic high-risk factors according to the type of pelvic LA. The extent of LA should be adjusted to reduce complications and not to affect adversely the prognosis of FIGO stage IB cervical cancer patients without pathologic high-risk factors.

Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer

We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.

Potential advantage of studying the lymphatic drainage by sentinel node technique and SPECT-CT image fusion for pelvic irradiation of prostate cancer

This study aims to investigate the in vivo drainage of lymphatic spread by using the sentinel node (SN) technique and single-photon emission computed tomography (SPECT)-computed tomography (CT) image fusion, and to analyze the impact of such information on conformal pelvic irradiation. Twenty-three prostate cancer patients, candidates for radical prostatectomy already included in a trial studying the SN technique, were enrolled. CT and SPECT images were obtained after intraprostate injection of 115 MBq of 99mTc-nanocolloid, allowing identification of SN and other pelvic lymph nodes. Target and nontarget structures, including lymph nodes identified by SPECT, were drawn on SPECT-CT fusion images. A three-dimensional conformal treatment plan was performed for each patient. Single-photon emission computed tomography lymph nodal uptake was detected in 20 of 23 cases (87%). The SN was inside the pelvic clinical target volume (CTV2) in 16 of 20 cases (80%) and received no less than the prescribed dose in 17 of 20 cases (85%). The most frequent locations of SN outside the CTV2 were the common iliac and presacral lymph nodes. Sixteen of the 32 other lymph nodes (50%) identified by SPECT were found outside the CTV2. Overall, the SN and other intrapelvic lymph nodes identified by SPECT were not included in the CTV2 in 5 of 20 (25%) patients. The study of lymphatic drainage can contribute to a better knowledge of the in vivo potential pattern of lymph node metastasis in prostate cancer and can lead to a modification of treatment volume with consequent optimization of pelvic irradiation.

Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies

The aim of this article is to report a preliminary analysis of our initial clinical experience with extended-field intensity-modulated radiotherapy for gynecologic malignancies. Between November 2002 and May 2005, 13 women with gynecologic malignancies were treated with extended-field radiation therapy. Of the women, 7 had endometrial cancer, 4 cervical cancer, 1 recurrent endometrial cancer, and 1 suspected cervical cancer. All women underwent computed tomography planning, with the upper vagina, parametria, and uterus (if present) contoured within the CTV. In addition, the clinical target volume contained the pelvic and presacral lymph nodes as well as the para-aortic lymph nodes. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events (CTCAE v 3.0). All late toxicity was scored using the Radiation Therapy Oncology Group late toxicity score. The median follow-up was 11 months. Extended-field intensity-modulated radiation therapy (IMRT) for gynecologic malignancies was well tolerated. Two patients experienced Grade 3 or higher toxicity. Both patients were treated with concurrent cisplatin based chemotherapy. Neither patient was planned with bone marrow sparing. Eleven patients had no evidence of late toxicity. One patient with multiple previous surgeries experienced a bowel obstruction. One patient with bilateral grossly involved and unresectable common iliac nodes experienced bilateral lymphedema. Extended-field-IMRT achieved good local control with only 1 patient, who was metastatic at presentation, and 1 patient not able to complete treatment, experiencing in-field failure. Extended-field IMRT is safe and effective with a low incidence of acute toxicity. Longer follow-up is needed to assess chronic toxicity, although early results are promising.

Magnetic Resonance Lymphography with Ferumoxtran-10 for Pelvic Lymph Node Target Delineation in Bladder and Prostate Cancer

Purpose/Objective: To determine the utility of Magnetic Resonance Imaging (MRI) with an ultra-small superparamagnetic iron oxide that delineates phagocytotic activity within lymph nodes as a means of lymph node target definition and to examine the patterns of lymph node metastases in prostate and bladder cancer to generate a nodal clinical target volume comprised of the nodal basins at risk of tumor spread. Materials/Methods: A single center trial was undertaken in 40 patients with histologically confirmed prostate (32) or bladder cancer (8). All patients underwent pre- and post- contrast MRI studies over two consecutive days. Axial images were obtained at 3 mm intervals through the pelvis. Ferumoxtran-10 (Combidex®: Advanced Magnetics, Inc, Cambridge, MA) was administered at 2.6 mg Fe/kg on the first day immediately after the initial MRI. The pelvic vasculature and lymph nodes were delineated from the origin of the inferior mesenteric artery to the ischial tuberosities using 3D modeling and image processing software (3D-DOCTOR®: Able Software Corp., Lexington, MA). Lymph node frequency and location relative to the adjacent vascular segments was analyzed. Nodes were ascertained to have metastases using previously demonstrated criteria and with clinicopathologic correlation in those patients undergoing pelvic lymph node dissection (Harisinghani et al. NEJM 2003;348:2491-9). The prostate cancer patients were treated with radiotherapy. However, patients with bladder cancer underwent radical cystectomy and pelvic lymph node dissection, allowing surgicopathologic correlation of the imaging results. Results: 40 patients were enrolled (see Table 1). In the patients with prostate cancer, 39 malignant nodes were identified. Metastases were situated in the following locations or vascular segments: obturator fossa (7); internal iliac (3); external iliac (11); common iliac (5); aortic/aortocaval (3); pararectal (6); and sacral (4). The median number of nodes excised at the time of cystectomy for those patients with bladder cancer was 29 (range 21 to 47). Pathologically, metastases were identified in the following locations or vascular segments: perivesicle (1); internal iliac (8); external iliac (6); common iliac (2); aortic/aortocaval (3); and pararectal (2). On post-contrast MRI imaging, a median of 27 (range 18 to 39) nodes was identified for both bladder and prostate cancer patients within the region occupied by the para-vesical, intercalating, para-rectal, pelvic sidewall, external iliac, common iliac, and pre-sacral lymph node basins. The maximum distance of these lymph nodes from the closest vessel was between 2.5 and 30 mm, with a mean distance of 7.5 mm.Table 1Patient Characteristics Conclusions: The use of MRI lymphography with ferumoxtran-10 provides an objective description of pertinent lymph node locations in a three-dimensional projection for pelvic IMRT and improves the precision of radiation treatment delivery. A uniform radial margin of expansion around the major pelvic vessels fails to adequately encompass all of the parietal and visceral lymph nodes at risk. Ferumoxtran-10 may be useful in the context of IMRT treatment planning as a means of identifying lymph nodes at risk of harbouring occult metastatic disease that should be included in the nodal CTV, and as a means of lowering the threshold for the detection of lymph node metastases that might be treated to a higher dose.

Magnetic resonance imaging of anal cancer

The purpose of this study was to evaluate the magnetic resonance imaging (MRI) appearances of primary and recurrent anal carcinoma, and to demonstrate the commonest patterns of local and distant disease spread. A retrospective review was performed of 27 cases of biopsy-proven anal carcinoma, where MRI was used for primary staging (9 patients) or suspected recurrence (18 patients). Two oncological radiologists reviewed the MR images, following a standardized approach. The size, extent and signal characteristics of the anal tumour were documented. Metastatic disease spread to lymph nodes, viscera and bone was recorded. In all, 7 patients with recurrent disease underwent surgery and subsequent histological correlation was performed. Primary and recurrent tumours were of high signal intensity relative to skeletal muscle on T2-weighted images (T2WI), and of low to intermediate signal intensity on T1-weighted images (T1WI). Lymph node metastases were of similar signal intensity to the anal cancer. Recurrent tumours were more locally advanced than primary tumours and extended into adjacent organs and the pelvic skeleton. Recurrent lymph node disease involved perirectal, presacral and internal iliac nodes more commonly than did primary lymph node disease. MRI can be useful in the primary staging of bulky tumours or of those with a long craniocaudal extent. MR has a role in the preoperative evaluation and surgical planning of cases of recurrent disease following radiotherapy.

Invasive vulvar cancer in a woman with human immunodeficiency virus: Case report and review of the literature

Background. HIV is associated with a decrease in cellular immunity which allows for persistence of high-risk HPV types and this can predispose the woman to dysplasia or cancer of the gynecologic tract. Case. We present a case of Stage 3 vulvar cancer in a 33-year-old HIV positive woman. The patient was treated with primary radiation; unfortunately there was persistent disease. Exenterative surgery was planned but abandoned due to a positive presacral node. Conclusion. The optimal treatment of advanced vulvar cancer in HIV positive patients remains unclear given the small number of cases reported in the literature. Lessons from the anal cancer literature may help inform the care of vulvar cancer patients given the comparable high prevalence of this disease in the patients infected with HIV.