Skin metastases of vulvar squamous cell carcinoma. Presentation of a rare case.

Skin metastases secondary to vulvar carcinoma is an infrequent clinical entity. The authors describe a case of squamous vulvar carcinoma, which presented with cutaneous involvement as a part of distant spread. After a radical vulvectomy, bilateral inguino-femoral lymphadenectomy, and adjuvant radiotherapy, the patient developed multiple cutaneous metastases in lower extremities. This case was unique in presentation, with skin metastases secondary from vulvar carcinoma, and indicated advance disease and poor prognosis.

Pathologic complete response in patients with localized soft tissue sarcoma treated with neoadjuvant therapy and its correlation with clinical outcomes: A systematic review.

Soft tissue sarcomas (STS), comprising approximately 1% of adult solid malignancies, are primarily treated with surgery, with the choice of perioperative treatment being a challenging and highly individualized decision. Clinical trials assessing neoadjuvant modalities in STS predominantly use clinical outcomes or radiologic response as endpoints, with pathologic complete response (pCR) not being employed as a designated study endpoint. Our systematic review aimed to assess the rates of pCR in clinical trials of different neoadjuvant modalities for STS and its correlation with patient clinical outcomes. 23 phase I, II and III studies were included, from which data regarding rates of pCR with each treatment, as well as correlation of pCR with clinical outcomes were retrieved. In 16 trials that assessed pCR, the percentage of patients who achieved a pCR ranged from 8 to 58%. Most of these trials did not aim to establish an association between pCR and clinical outcomes. However, among those that did investigate this correlation, a positive association was identified between pCR and both 5-year disease-specific survival (DSS) and 5-year overall survival (OS). While pCR serves as a crucial marker guiding treatment decisions in other neoplasms like triple negative breast cancer and urothelial cancer, it is not yet used in a similar setting for STS. Our findings indicate variability in patients achieving pCR across different neoadjuvant treatments for STS and a possible positive correlation with patient outcomes. Consequently, we propose considering pCR as a surrogate endpoint in future prospective trials for STS.

Evaluation of efficacy and toxicity in two different hypofractionated 3D-conformal external beam radiotherapy schedules in localised muscle invasive bladder cancer.

PURPOSE: To evaluate the efficacy as well as acute and late toxicity of two different accelerated hypofractionated 3D-conformal radiotherapy (Hypo-3DCRT) schedules in patients with bladder cancer. METHODS: Between February 2006 and June 2011, 50 elderly patients with cT1-2N0 bladder carcinoma were treated with Hypo-3DCRT. Mean age was 75 years. All patients were medically inoperable, with poor performance status, who couldn't tolerate either cystectomy or radical external beam irradiation on a daily basis. A dose of 36 Gy in 6 weekly fractions (arm A, N=39) or 39.96 Gy of 3.33 Gy twice daily, once a week, for 6 weeks (arm B, N=11) were prescribed. The primary study endpoints were the evaluation of acute/late gastrointestinal (GI) toxicity according to the EORTC/RTOG scale together with the visual analogue bladder-related pain score (VAS). RESULTS: The GI acute toxicities were: grade 1: arm A 24/39 (61.5%), arm B 9/11 (81.8%); grade 2: arm A 14/39 (35.9%), arm B 1/11 (9.1%); grade 3: arm A 1/39 (9.1%) (x(2), p=0.29). Only grade 1 late GI toxicity was seen and was significantly higher in arm A: arm A 17/39 (43.6%) and arm B 1/11 (9.1%) (x(2), p=0.037). The reduction of VAS score was similar in both arms (p=0.065). The median relapse free survival (RFS) was 15 and 16 months for arm A and B, respectively (log rank, p=0.71). CONCLUSIONS: Beyond the non-randomized design of the trial, the Hypo-3DCRT schedules used appear to be an acceptable alternative to the traditional longer radiotherapy (RT) schedules for elderly patients unfit for daily irradiation.

SYNCHRONOUS DIAGNOSIS OF TESTICULAR AND THYROID CANCER IN A YOUNG MALE.

Testicular cancer is the most common neoplasm in young males. The early diagnosis and the appropriate treatment make it a curable malignancy in over 90% of the patients, but 6% of the patients with testicular cancer develop a second, mostly treatment-related, malignancy in another primary site many years after the first diagnosis. The simultaneous appearance of a testicular tumor with another primary neoplasm is rarely described in the literature. Here is presented an interesting case of a coexisting non-seminomatous germ cell testicular tumor with a papillary thyroid carcinoma, which was detected early during post-treatment restaging of the testicular tumor. The synchronous presence of these two neoplasms might indicate a probable common pathogenetic background. As treatment-related oncogenesis is highly improbable in this case and the common environmental factors are not known yet, the interest is focused on genetic predisposition. Recent discoveries in molecular genetics show that the two neoplasms share common genetic alterations in the RAS and BRAF genes, which affect the significant signaling pathways. Interestingly, BRAF-V600E was positive in both primary malignancies in our individual.

Metastatic bone involvement in vulvar cancer: report of a rare case and review of the literature.

PURPOSE: Bone metastasis secondary to vulvar carcinoma is an infrequent clinical entity. Only ten cases have been published in the literature. We describe a case of squamous vulvar carcinoma, that presented with cervical vertebral involvement, as a part of distant spread. CASE: A 69-year-old woman presented with radicular pain and a painful cervical mass. MRI of the cervical spine was performed, showing an osteolytic lesion with spinal cord compression. CONCLUSION: This case was unique in presenting vertebral metastasis eight months after chemotherapy and radiotherapy.

Meta-analysis of the predictive value of KRAS mutations in treatment response using cetuximab in colorectal cancer.

PURPOSE: The monoclonal antibody cetuximab that targets epidermal growth factor receptor (EGFR) has been found effective in the treatment of colorectal cancer. However, mutations in exons 12 and 13 of KRAS oncogene have been reported as negative predictive factors for the treatment response using cetuximab. The purpose of this study was to conduct a meta-analysis of the published studies investigating the predictive value of KRAS mutations in the efficacy of cetuximab in patients suffering from colorectal cancer. METHODS: A systematic search of the literature was performed in PubMed, Medline, and Cochrane databases. Sensitivities, specificities and predictive values (negative and positive) of KRAS mutations as regards treatment response were calculated. RESULTS: Twenty-six studies were initially found during the literature search. After thorough evaluation, 13 papers were excluded for various reasons. Therefore, 13 studies were included in the present meta-analysis. In these studies, specificities were found much higher than sensitivities. Combining the data from the 13 studies, it was found that KRAS mutations comprise a negative predictive biomarker for response to cetuximab with very high specificity (0.96; 95% CI 0.84-0.99), and low sensitivity (0.47; 95% CI 0.43-0.50). Finally, the publication bias was found statistically significant. CONCLUSION: The results of the present meta-analysis suggest that cetuximab should be administered only to patients with colorectal cancer who have the wild type (KRASw) oncogene. Mutations in the KRAS gene are a negative predictive factor for response to cetuximab with very high specificity and low sensitivity. The latter may very well be attributed to additional mechanisms of resistance to anti-EGFR therapies such as mutations in BRAF.

Radiotherapy for Hodgkin's lymphoma: too hard to die?

The treatment of Hodgkin's lymphoma (HL) is associated with significant toxicity. The objective of high quality management is to keep the concept of combined modality, while trying to decrease the radiation dose, to diminish to a great extent the irradiated volume and at the same time to reduce the number of chemotherapy courses, introducing the so-called optimisation. New directives should be followed to obtain more effective treatments of HL. Shorter cycles of chemotherapy and the utilization of modern techniques in radiotherapy (RT) constitute fundamental steps to achieve this objective. Analysis of randomized studies supports the inclusion of reduced-field and dose of RT in the radiotherapeutic treatment options for HL. RT is an integral part of the combined-modality therapy (CMT) of HL.

Hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of primary advanced and recurrent ovarian cancer: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: Ovarian cancer is the most lethal gynecologic malignancy. Although treatment with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results, its role remains elusive. The aim of this study was to assess the comprehensive randomized evidence for the use versus non-use of HIPEC in primary and recurrent ovarian cancer. MATERIALS AND METHODS: The Medline, Embase and Cochrane databases, as well as the European Society for Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) conference abstracts of the last 5 years, were scrutinized in January 2022 for randomized, controlled trials that studied the use of HIPEC in ovarian cancer. Overall survival (OS), disease-free survival (DFS) and progression-free survival, as well as post-operative morbidity were the outcomes of interest. This study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. RESULTS: Six randomized, controlled trials that randomized 737 patients were included in our analysis; of these, four studies (519 patients) were in primary and two (218 patients) in recurrent settings. In primary ovarian cancer, the combination of HIPEC with interval cytoreductive surgery (CRS) and neoadjuvant chemotherapy significantly improved the 5-year OS [393 patients, risk ratio (RR) = 0.77; 95% confidence interval (CI) 0.67-0.90; P value = 0.001] and DFS (hazard ratio = 0.60; 95% CI 0.41-0.87; P value = 0.008) compared with standard treatment alone. In the absence of neoadjuvant chemotherapy, the use of HIPEC + CRS was not associated with any survival advantage (126 patients, 4-year OS, RR = 0.93; 95% CI 0.57-1.53; P value = 0.781), but the sample size was smaller in this subset. Use of HIPEC in recurrent ovarian cancer did not provide any survival advantage (5-year OS: 218 patients, RR = 0.85; 95% CI 0.45-1.62; P value = 0.626). The risk for grade ≥3 adverse events was similar between HIPEC and no HIPEC (RR = 1.08; 95% CI 0.98-1.18; P value = 0.109). CONCLUSIONS: In primary ovarian cancer the combination of HIPEC with interval CRS and neoadjuvant chemotherapy is a safe option that significantly improved 5-year OS and DFS. Its use in other settings should continue to be considered investigational.

Desmoplastic small round-cell tumour of the peritoneal cavity: case report and literature review.

Desmoplastic small round-cell tumour is a very rare neoplasm, which usually arises from the abdominal or pelvic peritoneum of adolescents and young adults. Early diagnosis is difficult, because most tumours present with non-specific gastrointestinal symptoms after a long asymptomatic period. It is generally a very aggressive tumour, which grows rapidly with poor prognosis and an overall five-year survival rate of 15% despite multimodal treatment. Despite multiple treatment strategies, the management of desmoplastic small round-cell tumour still remains a clinical challenge and no consensus about a therapeutic protocol has been established. A 35-year-old man presented with mild abdominal pain, constipation and weight gain, and was eventually diagnosed with desmoplastic small round-cell tumour, which was shown to be limited to the abdomen. After incomplete debulking surgery, radiotherapy and chemotherapy, he developed multiple metastatic nodular foci in chest and the pleura and, unfortunately, he died due to disease progression.

Mucinous breast carcinoma with tall columnar cells.

Mucinous carcinoma of the breast represents 1%-4% of all breast cancers. The World Health Organization classification divides this type of tumour into three different subtypes: mucinous carcinoma, mucinous carcinoma with tall columnar cells (mucinous cystadenocarcinoma and columnar cell mucinous carcinoma) and signet ring cell carcinoma. A 74-year-old woman presented a tumour with inflammatory features in the upper outer quadrant of her left breast, 7 cm in diameter. The core biopsy showed infiltrating ductal carcinoma of no specific type. The tumour-node-metastasis clinical staging was T4cN3M0 (Stage IIIC). She received neoadjuvant chemotherapy, underwent left mastectomy with radical axillary resection and subsequently received radiotherapy and chemotherapy. The histological examination of the surgical specimen revealed two solid tumors in the tail of Spence, which corresponded to adenocarcinoma with high columnar cells. The patient died 16 months after the diagnosis, suffering from pulmonary metastases and anterior chest wall infiltration. A review of the literature revealed only 21 reports of mucinous carcinoma of the breast with tall columnar cells, including our case. This is only the third time that the specific histological type of columnar cell mucinous carcinoma has been reported in the literature.

Hypofractionated irradiation for gliomas with 45.5Gy in 13 fractions: a retrospective study.

AIM: The aim of the present retrospective study was to evaluate the efficacy and toxicity of a hypofractionated radiotherapy (HFRT) schedule for grade IV glioblastoma multiforme (GBM). METHODS: Fourteen elderly patients with KPS less than 70, received 13 fractions of 350cGy with 3D-conformal technique (3DCRT) and non-coplanar fields. Acute and late skin and CNS toxicity was graded according to EORTC/RTOG criteria. RESULTS: The median follow-up was 9 months. All patients completed the irradiation without interruptions due to toxicity and received temozolomide (TMZ) after the completion of 3DCRT. The KPS during RT and at follow-up was not significantly changed (P=0.108). The median overall survival was 7 months. No severe skin acute or late toxicity was noted. In terms of CNS toxicity, only one patient presented grade III toxicity requiring hospitalization for two days. The irradiation schedule of 45.5Gy in 13 fractions seems effective and without moderate or severe toxicity. CONCLUSION: The suggested HFRT schedule might be an alternative one, for elderly patients with dismal prognosis, unfit for six weeks of daily irradiation. Prospective studies are needed for further validation of our results, especially with the use of TMZ.

Complete remission of a reccurrent mesenteric liposarcoma with rare histological features following the administration of trabectedin.

The present study describes a rare case of a mesenteric liposarcoma that resulted in a complete remission (CR) following treatment with trabectedin (Yondelis®). The patient presented with abdominal pain and fever. An abdominal mass was identified that corresponded to a mixed-type high-grade mesenteric liposarcoma with wide areas of necrosis, areas of dedifferentiation and features of a leiomyosarcoma. Three months after the removal of the first mass, the patient underwent a second laparotomy, followed by treatment with doxorubicin and ifosfamide. Subsequently, the patient was started on therapy with trabectedin and a CR was noted following only four cycles of therapy. The best responses that are reported in the literature for cases of liposarcoma treated with trabectedin are mostly for liposarcomas of the myxoid/round cell type and are mainly partial responses. In the present study, trabectedin was used for the treatment of a mesenteric liposarcoma of mixed morphological features and a CR was achieved.

Sucralfate gel as a radioprotector against radiation induced dermatitis in a hypo-fractionated schedule: a non-randomized study.

External beam radiotherapy with high doses provokes many acute skin reactions, such as erythema and moist desquamation. Many topical preparations are used in radiation oncology departments in the skin care. Sucralfate humid gel, a colloidal physical form of the anti-ulcer drug sucralfate, promotes epithelial regeneration and activates cell proliferation. Based on this knowledge, we performed a non-randomized clinical trial to evaluate the efficacy of topical sucralfate gel in 30 breast cancer patients receiving postoperative accelerated hypofractionated photon beam therapy. The comparison was performed with 30 patients as historical controls. The acute reaction of the skin was significantly lower in the group receiving the sucralfate gel (p<0.05, Mann Whitney test), while 90% of the patients had no evidence of radiation induced skin toxicity. There was no sucralfate gel related toxicity reported by any patient in this study. More patients in a randomized way are needed for more definite results.

Clinical implementation of total skin electron beam (TSEB) therapy: a review of the relevant literature.

Total skin electron beam therapy has been in medical service since the middle of the last century in order to confront rare skin malignancies. Since then various techniques have been developed, all aiming at better clinical results in conjunction with less post-irradiation complications. In this article every available technique is presented in addition to physical parameters of technique establishment and common dose fractionation. This study also revealed the preference of the majority of institutes the last 20 years in "six dual field technique" at a high dose rate, which is a safe and effective treatment.

Hypofractionated radiotherapy in non small cell lung cancer: a review of the current literature.

Hypofractionated irradiation has an established role in the palliative treatment of patients with advanced medically inoperable non - small cell lung cancer (NSCLC ) and poor performance status. Also hypofractionated radiotherapy merits careful consideration in the curative treatment of patients with Stage I and II disease using contemporary technology. The biological effect of radiation on tumours is increased as the overall treatment time is shortened. Hypofractionated field radiotherapy offers acceptable palliation with minimal toxicity. The rates of palliation for hemoptysis , chest pain , cough and dyspnea reported from studies with very short regimen ( 8,5 Gy x 2 ), are comparable to those of other trials that used more protracted palliative treatment . The observed toxicity is minimal, and no cases of oesophagitis, pneumonitis, or radiation myelopathy developed. The minimal toxicity is a reflection of both the low biologic total dose and the tight RT design. Therefore the radiation side effects appear to be related to the technique of RT delivered rather than the patient's PS. Hence, widely believed dogmas concerning the tolerance of critical structures to conventionally fractionated doses, such as the dose-volume effect, total dose, and time (latency) dependency, has to be re-evaluated for hypofractionated radiation therapy. As well there is data suggesting that the small stages I - II NSCLC are likely to benefit from hypofractionated regimens too. Hypofractionated stereotactic radiotherapy is a new technically complex approach to the treatment of early-stage nonsmall cell lung cancer. It is capable to deliver much higher doses to the cancer than is possible with standard techniques, and as a result, rates of tumour control are high and similar to what can be achieved by surgical resection. Refinements of technique and dose as well as randomized data are required before stereotactic radiotherapy can be endorsed as a standard of care for patients with inoperable peripherally located T1 non small cell lung cancer. A clear advantage of the very short hypofractionated palliative regimen is that it allows patients with a short expected survival time to spend more of their remaining time away from the hospital.