Groin Irradiation Research Articles

Lymph Node Metastasis and Patterns of Recurrence in Vulvar Carcinoma: 10 Years' Single Center Experience.

Vulvar carcinoma is a relatively rare malignancy and there is a paucity of data, especially from India and other developing countries regarding the prognostic factors impacting recurrence and survival. A retrospective observational study was conducted in the Department of Gynecologic Oncology at a tertiary care, regional cancer institute, including all patients with carcinoma vulva who underwent surgery between 2009 and 2018. Demographic profile, surgical-pathological information, details of neo-adjuvant chemotherapy, adjuvant radiation and chemotherapy, and peri-operative complications were analyzed. Long-term follow-up data was gathered, with an evaluation of various prognostic factors impacting recurrence and overall survival outcome. Forty-five cases with mean age of 56.2years (range 29-82) were treated during the study period. Surgery was the initial treatment modality in 41 (91.1%) cases. Neo-adjuvant chemotherapy prior to surgery was given to four cases. After complete surgico-pathological staging, most patients had stage I disease (26 cases, 57.8%) and 22.2% had stage II disease. Owing to microscopic lymph node involvement, seven cases (15.6%) belonged to FIGO stage III disease. Two cases had stage IVA disease with fixed groin nodes. Adjuvant chemotherapy in the form of 5-fluoro uracil and cisplatin was administered to four out of the nine patients with nodal involvement. The remaining five were advised adjuvant groin radiation. At a median follow-up of 34months (range 2-114months), 12 cases (26.7%) experienced a recurrence and one case with stage IVA disease progressed during adjuvant chemotherapy. The 5-year overall survival was 76.6% and the 5-year disease-free survival was 69.6%. There were a total number of 10 deaths, of which seven were due to disease recurrence or progression and the remaining 30% of deaths were due to medical co-morbid conditions. Overall survival was negatively impacted by increasing age (age > 60years), number of positive nodes, presence of perinodal spread, and stage of the disease. Recurrence-free survival was significantly reduced in those with the presence of peri-nodal spread and lympho-vascular space invasion. The incidence of lymph node metastasis was found to be higher in patients with age > 60years, increasing tumor size, presence of lympho-vascular space invasion and the number of lymph nodes removed. In carcinoma vulva, treatment should be individualized with multidisciplinary cooperation. In our series, we found that the stage of disease, nodal positivity, and nodal positivity with extra-capsular spread were significant prognostic factors impacting survival on analysis. Lymph nodal positivity was associated with increasing tumour size, presence of lympho-vascular invasion, and patient age.

QS8: Fat Grafting Depletes Profibrotic Prrx1-positive Fibroblasts In Irradiated Skin And Mitigates Radiation-induced Groin Contracture

Purpose:Contracture is a long-term complication of radiotherapy (RT) that results from pathologic fibrosis of soft tissue in the radiation field. Fat grafting can regenerate fibrotic soft tissue by decreasing collagen density and reorganizing collagen fiber networks. Fibroblasts are the predominant cell involved in extracellular matrix (ECM) synthesis, and dermal fibroblasts possess distinct embryonic origins. We recently identified a profibrotic fibroblast in the mouse ventral dermis marked by embryonic expression of paired related homeobox 1 (Prrx1). Here we sought to investigate how fat grafting alters Prrx1-positive subpopulation distribution as well as functional contractures.Methods:Adult Prrx-1Cre;R26mTmG reporter mice (n=9) underwent whole body lethal irradiation with 9 Gy for hematopoietic depletion. Mice were immediately reconstituted with 2 million nucleated bone-derived cells from donor NSG (NOD.CB17-Prkdcsscid/J) mice via retro-orbital sinus injection. The success of reconstitution and immunodepletion was assessed by fluorescence-activated cell sorting (FACS) analysis of peripheral blood. After 4 weeks, 30 Gy was delivered to the right hindlimb in five fractionated doses to generate limb contracture. The irradiated, contracted limb was then grafted with 200 μl fresh human lipoaspirate and limb extension was measured over the subsequent 8 weeks, at which point skin was harvested for assessment of fibroblast subtypes for FACS and immunofluorescence. A group of mice with radiation-induced groin contracture did not undergo fat grafting and served as the control group.Results:FACS analysis indicated successful immunodepletion and engraftment by 3 weeks post bone marrow transplantation. At one month following groin irradiation, mice had developed significant right hind limb contracture with significantly reduced limb extension (****p≤0.0001). Histologically this was paralleled by thickening of the dermis, and substantial expansion of the fibrogenic Prrx-1-positive fibroblast subpopulation. While human fat graft volume retention was reduced over 8 weeks following implantation, this was associated with significantly improved in limb extension. The skin overlying the grafted fat showed reduced collagen density, as indicated by trichrome staining, as well as a reduction in the fibrogenic Prrx-1-positive fibroblast subpopulation by immunofluorescence imaging, as compared to the control mice.Conclusion:Here we show that fat grafting improves the extensibility of irradiated and contracted hind limbs and reverses radiation-induced skin fibrosis by both reducing the collagen content and by altering the composition of dermal fibroblast subpopulations. Specifically, fat grafting results in a depletion of the Prrx-1-positive fibroblast subpopulation. Further elucidating how this profibrotic fibroblast subpopulation is involved in ventral surface soft tissue fibrosis will facilitate development of novel strategies to treat/prevent debilitating late side-effect of radiotherapy.

Mucinous tubular and spindle cell carcinoma of the kidney: Five case reports and review of the literature.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare and polymorphic tumor, which has been previously considered to be a low-grade malignancy, predominantly occurring in women. To the best of our knowledge, MTSCC with bladder metastasis has never been reported. The current study presents five adult cases of MTSCC that included three male and two female patients. Among the male cases, two were of advanced stage, one with MTSCC and renal chromophobe cell carcinoma with bladder metastasis and the other with MTSCC with invasion of the renal vein. The other three cases with small masses were at an early stage. All five cases had a good prognosis and were without recurrence after several years of follow-up. A 70-year-old male with intermittent gross hematuria, intermittent renal colic, and groin radiation pain for a year (case 1), was incidentally detected to have a left renal density mass by total abdominal enhanced computed tomography scans. In the other four cases, renal masses were found by B-ultrasound. The patient in case 1 underwent a retroperitoneal laparoscopic radical nephroureterectomy with bladder cuff resection and transurethral resection of the bladder tumor, and received gemcitabine hydrochloride via intravesical instillation therapy plus cisplatin chemotherapy every 3 months. The patient in case 2 underwent an open left radical nephrectomy and renal pedicle lymph node dissection. The other three patients underwent a laparoscopic radical nephrectomy. All five patients had no recurrence or new metastasis in other organs after follow-up. In conclusion, the incidence of MTSCC in men and women is not as disparate as reported in previous publications. The characteristics of the images of the five adult cases in the present study showed a considerable consistency, with only minor differences. The malignancy and prognosis of MTSCC are still controversial, and thus inclusion and review of more cases is required to reach a definite final conclusion. Sunitinib and gemcitabine chemotherapy in combination with cisplatin may be effective for the therapy of MTSCC patients with metastasis, but a larger range of treatments needs to be identified.

Abstract 38: Fat Grafting Rescues Radiation-induced Groin Contracture And Results In Diminished Numbers Of Profibrotic Prrx1-positive Dermal Fibroblasts

Purpose: Contracture is a long-term complication of radiotherapy (RT) that results from pathologic fibrosis of soft tissue in the radiation field. Fat grafting can regenerate fibrotic soft tissue by decreasing collagen density and reorganizing collagen fiber networks. Fibroblasts are the predominant cell involved in extracellular matrix (ECM) synthesis, and dermal fibroblasts possess distinct embryonic origins. We recently identified a profibrotic fibroblast in the mouse ventral dermis marked by embryonic expression of paired related homeobox 1 (Prrx1). Here we sought to investigate how fat grafting alters Prrx1-positive subpopulation distribution as well as functional contractures. Methods: Adult Prrx-1Cre;R26mTmG reporter mice (n=9) underwent whole body lethal irradiation with 9 Gy for hematopoietic depletion. Mice were immediately reconstituted with 2 million nucleated bone-derived cells from donor NSG (NOD.CB17-Prkdcsscid/J) mice via retro-orbital sinus injection. The success of reconstitution and immunodepletion was assessed by fluorescence-activated cell sorting (FACS) analysis of peripheral blood. After 4 weeks, 30 Gy was delivered to the right hindlimb in five fractionated doses to generate limb contracture. The irradiated, contracted limb was then grafted with 200 μl fresh human lipoaspirate and limb extension was measured over the subsequent 8 weeks, at which point skin was harvested for assessment of fibroblast subtypes for FACS and immunofluorescence. A group of mice with radiation-induced groin contracture did not undergo fat grafting and served as the control group. Results: FACS analysis indicated successful immunodepletion and engraftment by 3 weeks post bone marrow transplantation. At one month following groin irradiation, mice had developed significant right hind limb contracture with significantly reduced limb extension (****p≤0.0001). Histologically this was paralleled by thickening of the dermis, and substantial expansion of the fibrogenic Prrx-1-positive fibroblast subpopulation. While human fat graft volume retention was reduced over 8 weeks following implantation, this was associated with significantly improved in limb extension. The skin overlying the grafted fat showed reduced collagen density, as indicated by trichrome staining, as well as a reduction in the fibrogenic Prrx-1-positive fibroblast subpopulation by immunofluorescence imaging, as compared to the control mice. Conclusion: Here we show that fat grafting improves the extensibility of irradiated and contracted hind limbs and reverses radiation-induced skin fibrosis by both reducing the collagen content and by altering the composition of dermal fibroblast subpopulations. Specifically, fat grafting results in a depletion of the Prrx-1-positive fibroblast subpopulation. Further elucidating how this profibrotic fibroblast subpopulation is involved in ventral surface soft tissue fibrosis will facilitate development of novel strategies to treat/prevent debilitating late side-effect of radiotherapy.

Corrigendum to: Squamous cell carcinoma of the anal canal: a review of the aetiology, presentation, staging, prognosis and methods available for treatment.

Anal cancer is an uncommon malignancy, with the majority of cases comprised of squamous cell carcinomas. The increasing incidence of this disease reflects a rise in the transmission of the human papillomavirus, the causative organism of most tumours. Abdominoperineal resection (APR), once the primary mode of treatment, has been supplanted by sphincter-saving combination chemoradiation as the first-line therapy. However, surgeons continue to play a role in the multidisciplinary management of patients with anal cancer for diagnosis and post-treatment surveillance. Sentinel node biopsy may identify patients with clinically and radiographically negative inguinal lymph nodes who will benefit from groin irradiation. In very select cases, the controversial means of local excision has been employed as primary treatment, often in conjunction with radiation and chemotherapy. The management of persistent or recurrent anal cancers following primary chemoradiation remains a concern, for which only salvage APR currently offers the possibility of a cure. The introduction of human papillomavirus vaccines presents the exciting potential for the eradication of the disease.

Distal Vaginal Recurrences after Vaginal Brachytherapy

Distal Vaginal Recurrences after Vaginal Brachytherapy

Inguinal Lymph Node Recurrence in the Untreated Groin of Patients with Anal Carcinoma

Inguinal lymph node metastasis is predictive of locoregional recurrence and poor overall survival in anal carcinoma. Metachronous lymph node metastasis occurs in 10% of all anal cancer patients, but multiple studies have shown that the benefit of elective irradiation of the groin depends on T-stage, and the toxicity of groin irradiation must not be underestimated. To analyze the inguinal recurrence rates among patients with anal carcinoma (T1-4, N0-1) who did not receive elective irradiation therapy to the groin and to determine predictors of inguinal recurrence. Data on 119 patients treated between 1987 and 2005 were retrospectively analyzed. Patients were treated with 3-dimensional radiotherapy. The median dose was 60 Gy. During radiotherapy, 108 patients also received chemotherapy (5-fluorouracil and mitomycin-C). AJCC staging showed a distribution of 21 T1 (18%), 58 T2 (49%), 27 T3 (23%), 13 T4 (11%), 101 N0 (85%) and 18 N1 (15%) tumors. The median follow up was 65 months (range, 1-240 months). The 5-year inguinal recurrence rate was 0% for T1, 10% for T2, 21% for T3 and 19% for T4 tumors (p = 0.034). T2 tumors of the perianal skin and the anal canal had 5-year inguinal recurrence rates of 12% and 8%, respectively. The 5-year inguinal recurrence rate was 21% for tumors ≥4 cm vs. 2% for tumors <4 cm in size (p = 0.003). Eleven patients did not receive chemotherapy. Elective irradiation of the groin should be considered for local control in patients (N0-N1) with T2 tumors ≥4 cm in size and/or located in the perianal skin, and in all patients with T3 and T4 tumors.

Palliative chemotherapy in carcinoma penis: Does platinum and taxane combination holds a promise?

Aim:To report safety and efficacy of chemotherapy incorporating the combination of paclitaxel and platinum in patients with advanced penile carcinoma.Materials and Methods:Retrospective analysis of patient with advanced penile carcinoma undergoing palliative chemotherapy with paclitaxel and platinum combination. The demographic profile, indication of treatment, chemotherapy details, toxicity and survival outcome were noted. Statistical analysis was done for estimation of progression free survival and overall survival. Factors affecting these outcomes were sought for.Results:Eighteen patients with a median age of 47.5 years (31-68 years) were offered palliative intent chemotherapy over a period of 2.5 years. ECOG performance was 1 in 12 patients (66.7%) and 2 in 6 patients (33.3%). The grade of tumor was poorly differentiated in 8 patients (44.4%), moderately differentiated in 5 (27.8%) and we1l differentiated in 5 patients (27.8%). Twelve patients had previous surgical treatment (66.7%), with 2 of them having received groin radiation in past. The indication for treatment was metastatic disease in 7 patients (38.9%) and locally advanced disease in 11 patients (61.1%). Out of 18 patients 13 received chemotherapy. Paclitaxel and carboplatin combination was given in 10 patients (76.9%) while paclitaxel and cisplatin was received by 3 patients (23.1%). The median numbers of cycles received were 3 (1-6 cycles). Response rate was 30.8%. The median estimated progression free survival (PFS) and overall survival (OS) for patients receiving atleast one cycle of chemotherapy (n = 13) were 96 days and 246 days respectively. Among tested variables the median OS in patients who had received 2 or more cycles was 351 days versus 55 days in those who received less than 2 cycles (P = 0.025). However, after applying Bonferroni correction, the difference was no longer significant. There was no toxicity related death or life threatening complication.Conclusion:Our institutional protocol of platinum-based doublet with paclitaxel is effective, well-tolerated and has the advantage being delivered on an outpatient basis alone. Overall, we believe that paclitaxel-platinum is an effective regimen that needs to be investigated further in larger studies.

Squamous cell carcinoma of the anal canal: a review of the aetiology, presentation, staging, prognosis and methods available for treatment

Anal cancer is an uncommon malignancy, with the majority of cases comprised of squamous cell carcinomas. The increasing incidence of this disease reflects a rise in the transmission of the human papillomavirus, the causative organism of most tumours. Abdominoperineal resection (APR), once the primary mode of treatment, has been supplanted by sphincter-saving combination chemoradiation as the first-line therapy. However, surgeons continue to play a role in the multidisciplinary management of patients with anal cancer for diagnosis and post-treatment surveillance. Sentinel node biopsy may identify patients with clinically and radiographically negative inguinal lymph nodes who will benefit from groin irradiation. In very select cases, the controversial means of local excision has been employed as primary treatment, often in conjunction with radiation and chemotherapy. The management of persistent or recurrent anal cancers following primary chemoradiation remains a concern, for which only salvage APR currently offers the possibility of a cure. The introduction of human papillomavirus vaccines presents the exciting potential for the eradication of the disease.

New approach to anal cancer: Individualized therapy based on sentinel lymph node biopsy

Oncological treatment is currently directed toward a tailored therapy concept. Squamous cell carcinoma of the anal canal could be considered a suitable platform to test new therapeutic strategies to minimize treatment morbidity. Standard of care for patients with anal canal cancer consists of a combination of radiotherapy and chemotherapy. This treatment has led to a high rate of local control and a 60% cure rate with preservation of the anal sphincter, thus replacing surgical abdominoperineal resection. Lymph node metastases represent a critical independent prognostic factor for local recurrence and survival. Mesorectal and iliac lymph nodes are usually included in the radiation field, whereas the inclusion of inguinal regions still remains controversial because of the subsequent adverse side effects. Sentinel lymph node biopsies could clearly identify inguinal node-positive patients eligible for therapeutic groin irradiation. A sentinel lymph node navigation procedure is reported here to be a feasible and effective method for establishing the true inguinal node status in patients suffering from anal canal cancer. Based on the results of sentinel node biopsies, a selective approach could be proposed where node-positive patients could be selected for inguinal node irradiation while node-negative patients could take advantage of inguinal sparing irradiation, thus avoiding toxic side effects.

Quality of life and tumor control after short split-course chemoradiation for anal canal carcinoma

PurposeTo evaluate quality of life (QOL) and outcome of patients with anal carcinoma treated with short split-course chemoradiation (CRT).MethodsFrom 1991 to 2005, 58 patients with anal cancer were curatively treated with CRT. External beam radiotherapy (52 Gy/26 fractions) with elective groin irradiation (24 Gy) was applied in 2 series divided by a median gap of 12 days. Chemotherapy including fluorouracil and Mitomycin-C was delivered in two sequences. Long-term QOL was assessed using the site-specific EORTC QLQ-CR29 and the global QLQ-C30 questionnaires.ResultsFive-year local control, colostomy-free survival, and overall survival were 78%, 94% and 80%, respectively. The global QOL score according to the QLQ-C30 was good with 70 out of 100. The QLQ-CR29 questionnaire revealed that 77% of patients were mostly satisfied with their body image. Significant anal pain or fecal incontinence was infrequently reported. Skin toxicity grade 3 or 4 was present in 76% of patients and erectile dysfunction was reported in 100% of male patients.ConclusionsShort split-course CRT for anal carcinoma seems to be associated with good local control, survival and long-term global QOL. However, it is also associated with severe acute skin toxicity and sexual dysfunction. Implementation of modern techniques such as intensity-modulated radiation therapy (IMRT) might be considered to reduce toxicity.

Limited Value of Staging Squamous Cell Carcinoma of the Anal Margin and Canal Using the Sentinel Lymph Node Procedure: A Prospective Study with Long-Term Follow-Up

BackgroundSelection of patients with anal cancer for groin irradiation is based on tumor size, palpation, ultrasound, and fine needle cytology. Current staging of anal cancer may result in undertreatment in small tumors and overtreatment of large tumors. This study reports the feasibility of the sentinel lymph node biopsy (SLNB) in patients with anal cancer and whether this improves the selection for inguinal radiotherapy.MethodsA total of 50 patients with squamous anal cancer were evaluated prospectively. Patients without a SLNB (n = 29) received irradiation of the inguinal lymph nodes based on lymph node status, tumor size, and location of the primary tumor. Inguinal irradiation treatment in patients with a SLNB was based on the presence of metastases in the SLN.ResultsSLNs were found in all 21 patients who underwent a SLNB. There were 5 patients (24%) who had complications after SLNB and 7 patients (33%) who had a positive SLN and received inguinal irradiation. However, 2 patients with a tumor-free SLN and no inguinal irradiation developed lymph node metastases after 12 and 24 months, respectively.ConclusionsWe conclude that SLNB in anal cancer is technically feasible. SLNB can identify those patients who would benefit from refrain of inguinal irradiation treatment and thereby reducing the incidence of unnecessary inguinal radiotherapy. However, because of the occurrence of inguinal lymph node metastases after a tumor-negative SLNB, introduction of this procedure as standard of care in all patients with anal carcinoma should be done with caution to avoid undertreatment of patient who otherwise would benefit from inguinal radiotherapy.

Inguinal lymph node metastases are recognized with high frequency in rectal adenocarcinoma invading the dentate line. The histological features at the invasive front may predict inguinal lymph node metastasis

Inguinal lymph node (ILN) metastasis occurs with high frequency in some of the patients with lower rectal cancer. The aim of this study was to identify risk factors for ILN metastasis in patients with low rectal adenocarcinoma. We retrospectively analysed 156 patients with lower rectal adenocarcinoma who underwent radical resection (R0) at a single institution. Twenty-five (16%) patients had a tumour that invaded the dentate line, seven of whom had ILN metastasis. Invasion of the dentate line was significantly associated with a high rate of ILN metastasis, worse prognosis and local recurrence than with a tumour not invading the dentate line (P = 0.03). A Cox proportional hazard regression analysis revealed the histological characteristics at the invading front (Hif) also to be a risk factor for ILN metastasis. Tumours which invade the dentate line have a high rate of ILN metastases and worse cancer specific end-points. The presence of poorly differentiated or mucinous adenocarcinoma components is an indication for bilateral groin irradiation.

Radiation Therapy Compared With Pelvic Node Resection for Node-Positive Vulvar Cancer

To report long-term survival and toxicity of radiation compared with pelvic node resection for patients with groin node-positive vulvar cancer. A Gynecologic Oncology Group protocol enrolled 114 patients randomly allocated to postoperative pelvic and groin radiation (45-50 Gy, n=59) or to ipsilateral pelvic node resection (n=55) after radical vulvectomy and inguinal lymphadenectomy. Retrospective analyses for 114 enrolled patients included both risk of progression and death after treatment and assessment of toxicity. Median age was 70 years. Median survivor follow-up was 74 months. The relative risk of progression was 39% in radiation patients (95% confidence interval [CI] 0.17-0.88, P=.02). Fourteen intercurrent deaths occurred after radiation as compared with only two after pelvic node resection, narrowing 6-year overall survival (51% compared with 41%, hazard ratio 0.61 [95% CI 0.30-1.3], P=.18). However, the cancer-related death rate was significantly higher for pelvic node resection compared with radiation (51% compared with 29% at 6 years, hazard ratio 0.49 [95% CI 0.28-0.87], P=.015). Six-year overall survival benefit for radiation in patients with clinically suspected or fixed ulcerated groin nodes (P=.004) and two or more positive groin nodes (P<.001) persisted. A ratio of more than 20% positive ipsilateral groin nodes (number positive/number resected) was significantly associated with contralateral lymph node metastasis, relapse, and cancer-related death. Late chronic lymphedema (16% compared with 22%) and cutaneous desquamation (19% compared with 15%) were balanced after radiation and pelvic node resection. Radiation after radical vulvectomy and inguinal lymphadenectomy significantly reduces local relapses and decreases cancer-related deaths. Late toxicities remained similar after radiation or pelvic node resection. I.

Lymphatic mapping and sentinel lymph node biopsy in epidermoid carcinoma of the anal canal

Aim Although 15–25% of patients with anal cancer present with superficial inguinal lymph node metastases but the routine application of groin irradiation is controversial because of serious side effects. Inguinal sentinel lymph node biopsy (SLNB) can be used to select patients appropriately for inguinal radiation. The study evaluates the efficiency and clinical impact of SLNB. Methods Forty patients with anal cancer underwent 1 ml Tc 99m-Nanocolloid injection in four sites around the tumour. Patients with inguinal radio colloid enrichment were selected for sentinel lymph node biopsy (SLNB). Lymph node status was examined by haematoxylin and eosin (H&E) as well as immunohistochemistry-staining. All SLN-positive patients were scheduled for inguinal radiation; SLN-negative patients with T1 and early T2 tumours were not scheduled for inguinal radiation. Results SLN were detected in 36/40 patients. Three common patterns of lymphatic drainage were observed: mesenterial, iliacal and inguinal. Twenty patients with inguinal SLN underwent SLN-biopsy. 6/20 patients were SLN-positive. In 10/20 patients SLNB altered the therapy plan – four patients with T1-tumours and positive SLN had additional groin irradiation, whereas 6 patients with small T2-tumors and tumour-free inguinal SLN did not undergo inguinal irradiation. Conclusions Inguinal sentinel node biopsy in anal cancer is efficient and could assist in the decision for inguinal radiation. The validity and safety of the proposed therapeutic algorithm has to be proven by a larger, prospective study.

Sentinel lymph node biopsy for gastrointestinal cancers

Sentinel lymph node biopsy (SLNB) in gastrointestinal-(GI)-tract cancer is not yet of clinical relevance. Nevertheless, the results in the upper GI-tract promise to be helpful to individualize the indication for surgical therapy. SLNB in colon cancer still fails to show high validity to predict the nodal status, but may be helpful to clarify the prognostic role of micrometastases/isolated tumor cells. In anal cancer SLNB is able to guide the indication for groin irradiation.

Combined modality therapy for patients with nodal metastases from melanoma

7518 Background: Patients treated for regional nodal metastases from melanoma are at risk of distant metastases, regional failure, and long-term toxicity. Present treatment algorithms do not account adequately for these competing risks. Methods: Between 1983 and 2003, 466 patients with melanoma nodal metastases were managed with lymphadenectomy and radiation, with or without systemic therapy. For this retrospective review, actuarial outcomes were calculated using the Kaplan-Meier method and multivariate analysis was done with the proportional hazards model. Results: Of the 466 patients, surgery was a therapeutic procedure for clinically apparent nodal disease in 434. Adjuvant radiation was delivered to all patients, generally using a hypofractionated regimen, and systemic therapy was delivered to 154 patients. With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The 5-year DSS, DFS, and DMFS rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year disease-specific and distant metastasis-free survival. For patients with more than 10 involved LN the 2-year rate of brain failure approached 45%. The 5-year regional (in basin) control rate for all patients was 89% and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The 5- and 10-year rates of symptomatic lymphedema were 9% and 11%, respectively, and varied according to nodal region. For patients with cervical, axillary or groin LN disease the corresponding rates of symptomatic lymphedema were 1%, 20%, and 27%, respectively (p <0.0001). Conclusions: Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of death from melanoma remains high and patients requiring groin irradiation are at risk of chronic lymphedema. The data indicate that the threshold for recommending aggressive regional therapy should account for the site of nodal disease and certain clinical-pathologic factors. Also, clinical investigation must focus on the high rate of brain failure in some of these patients. No significant financial relationships to disclose.

Yolk sac tumor of the vulva: a case report with long-term disease-free survival

Background Yolk sac tumor (YST) of the vulva is extremely rare. Seven cases of vulvar YST have been reported to the literature. Due to the rarity of tumors, the appropriate choice of treatment may remain unclear. Case A 30-year-old woman presented with a 3.5-cm right labial mass. Excisional biopsy showed YST with predominant solid pattern. Three weeks after excision, right inguinal lymph node biopsy revealed metastatic tumor. The serum alpha-fetoprotein (AFP) was not elevated. Cisplatin-based chemotherapy was administered, followed by pelvic and groin irradiation. The patient was free of disease 90 months after the diagnosis. Conclusion Local excision of tumor with adjuvant cisplatin-based chemotherapy can be justified for vulvar YST. Inguinal lymphadenectomy is recommended because metastasis may occur early. Adjuvant radiation therapy may help to control the disease. Tumor size of 5 cm or less may be a favorable prognostic factor. Serum AFP level may not be a sensitive marker for follow-up of vulvar YST.

Primary groin irradiation vs primary groin surgery for early vulvar cancer.

Despite changes in technique, morbidity after surgical treatment for vulvar cancer is considerable and mainly related to the groin dissection. Primary radiotherapy to the groin is expected to result in lower morbidity. However, studies on the efficacy of primary radiotherapy for the groins in terms of groin recurrences and survival show conflicting results. To determine whether the effectiveness and safety of primary radiotherapy to the inguino-femoral lymph nodes is comparable with surgery The literature search was carried out using the criteria set by the Cochrane Gynaecological Cancer Group. A MEDLINE and EMBASE search using the Mesh Heading 'vulvar neoplasms' and textword 'vulva' was performed. Publications on the effectiveness of primary radiotherapy treatment of early squamous cell carcinoma of the vulva were selected. Randomized clinical trials, case-control and observational studies of primary radiotherapy of the groin Type of participants: Patients with early squamous cell cancer of the vulva Type of interventions: inguino-femoral lymph node dissection and primary radiotherapy of the inguino-femoral lymph nodes. Type of outcome measurements: incidence of groin recurrences, survival and morbidity Two reviewers independently assessed study quality and extracted results Out of nine reviewed papers only three met the selection criteria. From these studies, (one randomised controlled trial [RCT] one case-control and one observational study) it became clear from the RCT that the incidence of groin recurrences after primary radiotherapy is higher compared with surgery. survival was also worse in the radiotherapy group. The other two studies showed a higher than expected number of groin recurrences after primary radiotherapy. Morbidity after primary radiotherapy was lower compared with surgery. The conclusion of the RCT was criticized on the grounds of the depth of the radiotherapy administered. The depth of 3 cm used in the RCT, is too shallow to administer an optimal dose to the deeper groin nodes. As shown in an RCT, primary radiotherapy to the groin results in less morbidity but also in a higher number of groin recurrences compared with surgery. Although the technique of radiotherapy in the RCT was criticized, other uncontrolled data do not give evidence for a similar or better groin control for radiotherapy when compared to surgery. This means that surgery is still to be considered the cornerstone of therapy for the groin nodes in women with vulvar cancer. Individual patients not fit enough to withstand surgery can be treated with primary radiotherapy.

Elective groin irradiation is not indicated for patients with adenocarcinoma of the rectum extending to the anal canal

Purpose: To evaluate the inguinal nodal failure rate in patients with locally advanced rectal cancer with anal canal involvement (ACI) treated with pelvic chemoradiation without elective inguinal irradiation.Methods and Materials: From 1990 and 1998, 536 patients received preoperative or postoperative chemoradiation for rectal cancer with curative intent; 186 patients had ACI (<4 cm from the anal verge on rigid proctoscopy). Two patients had positive inguinal nodes at presentation. Chemoradiation was delivered preoperatively (45 Gy in 25 fraction) or postoperatively (53 Gy in 29 fractions) with concurrent continuous infusion of 5-fluorouracil (300 mg/m2/d). The inguinal region was specifically irradiated in only 2 patients who had documented inguinal nodal disease.Results: The median follow-up was 50 months. Only 6 of 184 ACI patients who had clinically negative inguinal nodes at presentation developed inguinal nodal recurrence (5-year actuarial rate 4%); 4 of the 6 cases were isolated. Two patients underwent successful salvage. Only 1 died of uncontrolled groin disease. Local control was achieved in both patients with inguinal nodal disease at presentation, but both died of metastatic disease. Only 3 patients with tumors >4 cm from the verge developed inguinal recurrence (5-year actuarial rate <1%).Conclusions: Inguinal nodal failure in rectal cancer patients with ACI treated with neoadjuvant or adjuvant chemoradiation is not high enough to justify routine elective groin irradiation.