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Purpose: To establish the regional lymph node (LN) distribution probability map and draw the neck clinical target volume specific to nasopharyngeal carcinoma (NPC).Methods and Materials: One thousand patients with pathologically proven NPC were enrolled from January 2010 to December 2011. The center point of the LNs with a minimal axial diameter of ≥4 mm was marked on a single treatment planning computed tomography scan. The neck LN levels I to X using the 2013 updated international consensus guidelines were also contoured. LN distribution probability maps and distribution curves were established. The relationships between the LN distribution and consensus guidelines were analyzed to propose modifications for clinical target volume boundaries specific to NPC.Results: A total of 10,651 LNs from 959 patients were marked. Based on the distribution of LNs and consensus guidelines, most of the LN levels defined in the 2013 updated consensus guidelines were confirmed to be comprehensive and applicable for NPC. However, for level Vb, 13.3% of cases (11 of 83) had LNs beyond the posteromedial border. For level VIIa (retropharyngeal LN), 1.5% of cases (12 of 819) had LNs above the cranial boundary, and 5 cases had LNs that emerged in the medial group. Moreover, we confirmed that no LN had been detected in certain areas of levels Ib, II, IVa, and Vc. Accordingly, a new level VIIc was proposed to include the medial group of retropharyngeal LNs, moderately extended boundaries for levels Vb and VIIa were recommended, and reduced boundaries are possibly adaptable for levels Ib, II, IV, and Vc.Conclusions: Most LN levels in the 2013 updated consensus guidelines are comprehensive and applicable for NPC. We have proposed a new level VIIc to include a medial group of retropharyngeal LNs, recommended moderate extended boundaries for levels Vb and VIIa, and suggested that the boundaries for levels Ib, II, IV, and Vc might be reduced. [ABSTRACT FROM AUTHOR]

After vascular reconstructions in the groin area, a persistent lymph fistula regularly threatens the prognosis of the affected extremity. Rapid, effective treatment of the lymph fistula is therefore essential in order to be able to prevent amputation. As part of a pilot study, we wanted to analyze the chances and limitations of radiotherapy in the treatment of lymphatic fistulas. As part of an internal quality control, patients were identified for this study who acquired a lymph fistula in the groin as a result of vascular surgery due to peripheral artery disease stage IV and were irradiated at the University Hospital Düsseldorf. Eight men aged 66 + 12, 4 years underwent vascular surgery for PAD stage IV. Surgery was performed in these patients via the groin and all men subsequently had a persistent lymphatic fistula with a secretion greater than 50 ml/day. Five patients were irradiated with a fractionation of 10 × 0.4 Gy and 3 patients with a fractionation of 10 × 0.3 Gy. In all patients, the lymphatic fistula dried up within the irradiation series. No higher-grade complications occurred. Irradiation of the groin in the case of a persistent lymphatic fistula could be a therapeutic option to avoid amputations due to wound infections after vascular reconstruction in the groin. Prospective randomized studies would be desirable in order to be able to better evaluate the role of radiotherapy in the treatment of lymphatic fistulas. [ABSTRACT FROM AUTHOR]

Prophylactic lymphovenous bypass (LVB), in which a severed lymphatic channel is anastomosed to a low-pressure venule, is a microsurgical technique performed after axillary lymph node dissection (ALND) and intended to prevent breast cancer related lymphedema (BCRL). However, the location of these fragile anastomoses in related to radiotherapy (RT) fields remains unstudied. We aimed to identify the typical location of LVB anastomoses and evaluate the feasibility of shielding them from RT dose. Patients underwent LVB with the placement of a circular clip for identification following ALND and received RT at a single institution. Delineation of the target volumes and lymph nodes levels was performed using NRG atlases. Additionally, the axillary and lateral thoracic vessels junction (ALTJ) -previously correlated with BCRL development- was delineated. The LVB clip was contoured and a 0.5cm expansion used to define a LVB volume. RT plans were created with 3D CRT and VMAT. The mean maximum dose to the LVB volume was compared between the two groups using T Test. Five patients underwent the procedures described above; all underwent mastectomy, ALND and LVB. The LVB anastomoses were identified in axillary Level 1, immediately subjacent (caudal) to the ALTJ. Owing to their location in the tangent fields, the mean maximum dose to LVB volume was 47.2 Gy using 3D planning and 18.7 Gy using VMAT (p<0.0001). Prophylactic LVB following ALND is increasing in utilization. However, almost all patients undergoing ALND will also receive RT, and effect of RT on the viability of the LVB anastomoses is unknown. In this proof-of-concept study, the location of LVB was consistently identified in level 1 of the axilla. Owing to its location in the tangent fields, exclusion of the LVB volume was typically difficult with 3D CRT. VMAT allowed superior sparing of this structure. Further study is required to clarify the viability of the anastomoses after RT, their dose tolerance, and whether active dose avoidance is necessary. [ABSTRACT FROM AUTHOR]

An estimated 40% of breast cancer patients undergoing axillary lymph node dissection (ALND) and nodal radiation (RT) develop upper extremity breast cancer related lymphedema (BCRL.) The goal of the lymphatic microsurgical preventive healing approach (LYMPHA,) which creates a lymphatic venous anastomosis, reducing interstitial volume and improving lymphatic drainage, at the time of ALND is to mitigate the development of BCRL, thereby improving quality of life for breast cancer survivors. We hypothesize that patients who received LYMPHA will have lower rates of BCRL over those who did not receive LYMPHA. A total of 54 patients were retrospectively evaluated in this IRB approved study. All patients underwent axillary lymph node dissection and adjuvant regional nodal radiation. Twenty-seven patients underwent LYMPHA during their initial oncological surgery and a matched paired control cohort of 27 patients who did not undergo LYMPHA were evaluated. The average age of patients who did and did not undergo LYMPHA was 54 and 52, respectively. The total number of nodes dissected in patients that underwent LYMPHA versus those who did not was 17 and 15, respectively. The average BMI for patients that underwent LYMPHA versus those who did not was the same at 28 kg/m2 for both groups. The average mean dose to axillary levels I through III in all patients was 4124 cGy. The average max dose to axillary levels I through III in all patients was 4780 cGy. 7 patients in both groups developed breast cancer related lymphedema (BCRL). The average number of days status post last RT fraction for BCRL to develop/first clinical documentation was 462 and 571 days in the LYMPHA and no LYMPHA group, respectively. The rates of BCRL between the two groups were not different as initially hypothesized. One proposed reason for this is that patients on the LYMPHA protocol were monitored very closely for any signs of BCRL, while the matched control BCRL rates may be underestimated. This study warrants further investigation to be presented in a poster, as dosimetric evaluation may reveal sparing of particular portions of the lymphatic bypass can optimize outcomes in regard to BCRL. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the occurrence of positive lymph nodes on magnetic resonance lymphography (MRL) in patients with a prostate-specific antigen (PSA) recurrence after prostatectomy and to investigate the relation between score on the Stephenson nomogram and lymph node involvement on MRL. Methods and Materials: Sixty-five candidates for salvage radiation therapy were referred for an MRL to determine their lymph node status. Clinical and histopathologic features were recorded. For 49 patients, data were complete to calculate the Stephenson nomogram score. Receiver operating characteristic (ROC) analysis was performed to determine how well this nomogram related to the MRL result. Analysis was done for the whole group and separately for patients with a PSA <1.0 ng/mL to determine the situation in candidates for early salvage radiation therapy, and for patients without pathologic lymph nodes at initial lymph node dissection. Results: MRL detected positive lymph nodes in 47 patients. ROC analysis for the Stephenson nomogram yielded an area under the curve (AUC) of 0.78 (95% confidence interval, 0.61-0.93). Of 29 patients with a PSA <1.0 ng/mL, 18 had a positive MRL. Of 37 patients without lymph node involvement at initial lymph node dissection, 25 had a positive MRL. ROC analysis for the Stephenson nomogram showed AUCs of 0.84 and 0.74, respectively, for these latter groups. Conclusion: MRL detected positive lymph nodes in 72% of candidates for salvage radiation therapy, in 62% of candidates for early salvage radiation therapy, and in 68% of initially node-negative patients. The Stephenson nomogram showed a good correlation with the MRL result and may thus be useful for identifying patients with a PSA recurrence who are at high risk for lymph node involvement. [Copyright &y& Elsevier]

Purpose: To determine the clinical value of two novel molecular imaging techniques: 11C-choline positron emission tomography (PET)/computed tomography (CT) and ferumoxtran-10 enhanced magnetic resonance imaging (magnetic resonance lymphography [MRL]) for lymph node (LN) treatment in prostate cancer (PCa) patients. Therefore, we evaluated the ability of PET/CT and MRL to assess the number, size, and location of LN metastases in patients with primary or recurrent PCa. Methods and Materials: A total of 29 patients underwent MRL and PET/CT for LN evaluation. The MRL and PET/CT data were analyzed independently. The number, size, and location of the LN metastases were determined. The location was described as within or outside the standard clinical target volume for elective pelvic irradiation as defined by the Radiation Therapy Oncology Group. Subsequently, the results from MRL and PET/CT were compared. Results: Of the 738 LNs visible on MRL, 151 were positive in 23 of 29 patients. Of the 132 LNs visible on PET/CT, 34 were positive in 13 of 29 patients. MRL detected significantly more positive LNs (p < 0.001) in more patients than PET/CT (p = 0.002). The mean diameter of the detected suspicious LNs on MRL was significantly smaller than those detected by PET/CT, 4.9 mm and 8.4 mm, respectively (p < 0.0001). In 14 (61%) of 23 patients, suspicious LNs were found outside the clinical target volume with MRL and in 4 (31%) of 13 patients with PET/CT. Conclusion: In patients with PCa, both molecular imaging techniques, MRL and 11C-choline PET/CT, can detect LNs suspicious for metastasis, irrespective of the existing size and shape criteria for CT and conventional magnetic resonance imaging. On MRL and PET/CT, 61% and 31% of the suspicious LNs were located outside the conventional clinical target volume. Therefore, these techniques could help to individualize treatment selection and enable image-guided radiotherapy for patients with PCa LN metastases. [Copyright &y& Elsevier]

Purpose: To investigate the pattern of lymph node spread in prostate cancer patients with a biochemical recurrence after radical prostatectomy, eligible for salvage radiotherapy; and to determine whether the clinical target volume (CTV) for elective pelvic irradiation in the primary setting can be applied in the salvage setting for patients with (a high risk of) lymph node metastases. Methods and Materials: The charts of 47 prostate cancer patients with PSA recurrence after prostatectomy who had positive lymph nodes on magnetic resonance lymphography (MRL) were reviewed. Positive lymph nodes were assigned to a lymph node region according to the guidelines of the Radiation Therapy Oncology Group (RTOG) for delineation of the CTV for pelvic irradiation (RTOG-CTV). We defined four lymph node regions for positive nodes outside this RTOG-CTV: the para-aortal, proximal common iliac, pararectal, and paravesical regions. They were referred to as aberrant lymph node regions. For each patient, clinical and pathologic features were recorded, and their association with aberrant lymph drainage was investigated. The distribution of positive lymph nodes was analyzed separately for patients with a prostate-specific antigen (PSA) <1.0 ng/mL. Results: MRL detected positive aberrant lymph nodes in 37 patients (79%). In 20 patients (43%) a positive lymph node was found in the pararectal region. Higher PSA at the time of MRL was associated with the presence of positive lymph nodes in the para-aortic region (2.49 vs. 0.82 ng/mL; p = 0.007) and in the proximal common iliac region (1.95 vs. 0.59 ng/mL; p = 0.009). There were 18 patients with a PSA <1.0 ng/mL. Ten of these patients (61%) had at least one aberrant positive lymph node. Conclusion: Seventy-nine percent of the PSA-recurrent patients had at least one aberrant positive lymph node. Application of the standard RTOG-CTV for pelvic irradiation in the salvage setting therefore seems to be inappropriate. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the feasibility of magnetic resonance lymphography (MRL) –guided delineation of a boost volume and an elective target volume for pelvic lymph node irradiation in patients with prostate cancer. The feasibility of irradiating these volumes with a high-dose boost to the MRL-positive lymph nodes in conjunction with irradiation of the prostate using intensity-modulated radiotherapy (IMRT) was also investigated. Methods and Materials: In 4 prostate cancer patients with a high risk of lymph node involvement but no enlarged lymph nodes on CT and/or MRI, MRL detected pathological lymph nodes in the pelvis. These lymph nodes were identified and delineated on a radiotherapy planning CT to create a boost volume. Based on the location of the MRL-positive lymph nodes, the standard elective pelvic target volume was individualized. An IMRT plan with a simultaneous integrated boost (SIB) was created with dose prescriptions of 42 Gy to the pelvic target volume, a boost to 60 Gy to the MRL-positive lymph nodes, and 72 Gy to the prostate. Results: All MRL-positive lymph nodes could be identified on the planning CT. This information could be used to delineate a boost volume and to individualize the pelvic target volume for elective irradiation. IMRT planning delivered highly acceptable radiotherapy plans with regard to the prescribed dose levels and the dose to the organs at risk (OARs). Conclusion: MRL can be used to select patients with limited lymph node involvement for pelvic radiotherapy. MRL-guided delineation of a boost volume and an elective pelvic target volume for selective high-dose lymph node irradiation with IMRT is feasible. Whether this approach will result in improved outcome for these patients needs to be investigated in further clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: To compare the nodal risk formula (NRF) as a predictor for lymph node (LN) metastasis in patients with prostate cancer with magnetic resonance lymphography (MRL) using Ultrasmall Super-Paramagnetic particles of Iron Oxide (USPIO) and with histology as gold standard. Methods and Materials: Logistic regression analysis was performed with the results of histopathological evaluation of the LN as dependent variable and the nodal risk according to the NRF and the result of MRL as independent input variables. Receiver operating characteristic (ROC) analysis was performed to assess the performance of the models. Results: The analysis included 375 patients. In the single-predictor regression models, the NRF and MRL results were both significantly (p <0.001) predictive of the presence of LN metastasis. In the models with both predictors included, NRF was nonsignificant (p = 0.126), but MRL remained significant (p <0.001). For NRF, sensitivity was 0.79 and specificity was 0.38; for MRL, sensitivity was 0.82 and specificity was 0.93. After a negative MRL result, the probability of LN metastasis is 4% regardless of the NRF result. After a positive MRL, the probability of having LN metastasis is 68%. Conclusions: MRL is a better predictor of the presence of LN metastasis than NRF. Using only the NRF can lead to a significant overtreatment on the pelvic LN by radiation therapy. When the MRL result is available, the NRF is no longer of added value. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate indirect magnetic resonance lymphangiography (MR-LAG) using interstitial injection of conventional gadolinium contrast (gadoteridol and gadopentetate dimeglumine) for delineating the primary lymphatic drainage of head-and-neck sites. Methods and Materials: We performed head-and-neck MR-LAG in 5 healthy volunteers, with injection of dermal and mucosal sites. We evaluated the safety of the procedure, the patterns of enhancement categorized by injection site and nodal level, the time course of enhancement, the optimal concentration and volume of contrast, and the optimal imaging sequence. Results: The worst side effects of interstitial contrast injection were brief, mild pain and swelling at the injected sites that were self-limited. MR-LAG resulted in consistent visualization of the primary lymphatic drainage pattern specific to each injected site, which was reproducible on repeated examinations. The best enhancement was obtained with injection of small volumes (0.3-0.5 mL) of either agent diluted, imaging within 5-15 min of injection, and a three-dimensional fast spoiled gradient echo sequence with magnetization transfer. Conclusions: We found head-and-neck MR-LAG to be a safe, convenient imaging method that provides functional information about the lymphatic drainage of injected sites. Applied to head-and-neck cancer, it has the potential to identify sites at highest risk of occult metastatic spread for radiotherapy or surgical planning, and possibly to visualize micrometastases. [ABSTRACT FROM AUTHOR]

Purpose: Intensity-modulated radiotherapy for gynecologic malignancies requires proper knowledge of the volumes to be irradiated and accurate delineation of these volumes on a three-dimensional projection. In this study, assisted by lymphangiography (LAG), we derived guidelines for delineating nodal target volumes on CT.Methods and Materials: Sixteen patients with cervical cancer who underwent radiotherapy between 1995 and 1999 at the Mallinckrodt Institute of Radiology were enrolled in the study. The initial 6 patients underwent bipedal LAG as part of the staging workup. Cross-sectional CT images were acquired and analyzed, and lymph node locations were described relative to the aorta, vena cava, common iliac, external iliac, and femoral vessels. The greatest distance from lymph node to vessel wall and pelvic sidewall was determined for each nodal group. This served as a guideline from which the clinical target volume (CTV) definitions were developed. This proposed CTV was then applied to CT scans of 10 patients to determine the amounts of normal tissues encompassed.Results: Nodal CTV guidelines were derived to cover 100% of LAG-avid lymph nodes. This CTV definition encompassed an average of 58.1 ± 22.8 cm3 (6.8% ± 2.8% of total volume) small bowel, 28.4 ± 19.2 cm3 (4.2% ± 3.2%) large bowel, 8.6 ± 8.6 cm3 (3.2% ± 2.6%) bladder, and 1.6 ± 3.1 cm3 (1.0% ± 1.7%) rectum. The absolute volume and fraction of normal tissues encompassed by CTV plus 1- or 2-cm margins were calculated.Conclusion: This study presents the first time that three-dimensional lymph node mapping with the aid of LAG has been used to generate a nodal CTV guideline. This information may assist radiation oncologists in properly determining nodal target volumes and selecting a margin around the CTV for intensity-modulated radiotherapy. [Copyright &y& Elsevier]