Evaluating the Optimal Sequence of Treatment With EGFR Inhibitors and Bevacizumab in RAS Wild-Type Metastatic Colorectal Cancer.

Background Epithelial growth factor receptor inhibitors (EGFRi) and bevacizumab are the two main target therapies available for first-line treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC). However, the optimal sequencing of these agents remains unclear. In this study, we aimed to evaluate the optimal sequence with EGFRi and bevacizumab in first- and second-line treatment. Methods This was a retrospective cohort study with RAS wt mCRC patients identified by extended RAS analysis between 2013 and 2020 at a comprehensive cancer center. All patients had to be treated with a sequence of systemic treatment that included an EGFRi and bevacizumab in first and second line, in either order. Two groups were defined according to treatment sequence: first-line EGFRi followed by second-line bevacizumab (cohort A) or the reverse sequence (cohort B). Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival with first-line treatment (PFS1), progression-free survival with second-line treatment (PFS2), objective response rate (ORR), and serious adverse events (grade ≥ 3). Survival was estimated using the Kaplan-Meier method, and survival differences between groups were compared using the log-rank test. Univariate analyses were performed using Cox proportional hazard model. Results A total of 124 patients were included (93 in cohort A and 31 in cohort B). There were no statistical significant differences in median OS (A: 34.9 months vs B: 29.2 months; p=0.590), PFS1 (A: 13.1 months vs B: 8.2 months; p=0.600), and PFS2 (A: 7.4 months vs B: 5.5 months; p=0.110) between groups. No significant differences were also found between treatment sequences in subgroups defined by age, gender, primary tumor location, sidedness, timing of metastasis, number of metastatic sites, multimodal therapy, primary tumor resection, and first-line chemotherapy backbone. ORR was significantly higher with first-line treatment with EGFRi (A: 55.9% vs B: 22.6%; p=0.001). At the final follow-up, the proportion of patients with SAEs was similar between treatment sequences (p=0.827). Discussion Our study showed no impact of the treatment sequence with EGFRi and bevacizumab in the survival of RAS wt mCRC. However, patients treated with first-line EGFRi had significantly higher response rates, thus favoring its use in patients with symptomatic tumors and borderline resectable metastasis. Prospective trials are warranted to define the optimal sequence of treatment in RAS wt mCRC patients.

Eccrine Hidradenocarcinoma of the Scalp.

Eccrine hidradenocarcinoma is a rare adnexal neoplasm arising from the eccrine sweat glands of the skin. Surgery and radiotherapy are the mainstay of treatment, and chemotherapy is reserved for unresectable or metastatic lesions. We present the case of a 60-year-old man, referred for treatment of an unresectable basal cell carcinoma of the scalp. He started Vismodegib in January of 2017 but progressed after three months. A new biopsy showed a poorly differentiated carcinoma. The patient started carboplatin/paclitaxel with a major response, enabling surgery in December of 2017. Pathology concluded on a hidradenocarcinoma, R1, and radiotherapy was not possible due to local infection. Four months later, he underwent radiotherapy due to local recurrence, and restarted carboplatin/paclitaxel, but with progressive disease. An exploratory surgery in October of 2018 revealed unresectable disease. Restaging showed lung metastasis and second-line chemotherapy was proposed. However, due to continued clinical deterioration, the patient died in February of 2019.

Merkel cell carcinoma metastatic to the testis: report of a rare diagnosis and review of the literature.

Merkel cell carcinoma is an aggressive malignancy that frequently recurs/disseminates, but metastases to the genitourinary tract are rare. Only eight cases of Merkel cell carcinoma metastatic to the testis are reported. We describe the ninth case of this event and provide a review of the literature. A 58-year-old man diagnosed with Merkel cell carcinoma of the wrist, presented, 37 months later, a recurrence in the form of a testicular metastasis. The tumor consisted of a monotonous proliferation of small, blue, round cells, with immunoexpression of neuroendocrine markers and the typical dot-like paranuclear immunostaining for cytokeratin 20, in the absence of immunostaining for cytokeratin 7. The patient is alive with no evidence of disease. Clinicians should be aware of the possibility of metastatic dissemination to the testis since genital examination/imaging is not part of routine follow-up for these patients, but timely orchiectomy may be curative.

Merkel cell carcinoma metastatic to the testis: report of a rare diagnosis and review of the literature

Merkel cell carcinoma is an aggressive malignancy that frequently recurs/disseminates, but metastases to the genitourinary tract are rare. Only eight cases of Merkel cell carcinoma metastatic to the testis are reported. We describe the ninth case of this event and provide a review of the literature. A 58-year-old man diagnosed with Merkel cell carcinoma of the wrist, presented, 37 months later, a recurrence in the form of a testicular metastasis. The tumor consisted of a monotonous proliferation of small, blue, round cells, with immunoexpression of neuroendocrine markers and the typical dot-like paranuclear immunostaining for cytokeratin 20, in the absence of immunostaining for cytokeratin 7. The patient is alive with no evidence of disease. Clinicians should be aware of the possibility of metastatic dissemination to the testis since genital examination/imaging is not part of routine follow-up for these patients, but timely orchiectomy may be curative.

Basal cell carcinoma: multimodal treatment and the role of neoadjuvant vismodegib

Basal cell carcinoma (BCC) is the most common skin cancer. It generally has an indolent course with low rates of metastasis and mortality. However, BCC is locally invasive and can cause significant morbidity due to destructive local spread. We report our experience with a patient who was referred to our skin cancer unit due to a previously neglected lesion on the parietal region of the scalp, which had developed for 7 years. The patient was prescribed vismodegib on the basis that surgery could cause excessive functional and aesthetic damage. The patient had an objective partial response after 20 months of treatment. He was then submitted to radical skin excision, leaving a large defect that was reconstructed using a free latissimus dorsi muscle flap. The patient recovered well, and at the 1-year follow-up there were no signs of local recurrence. Our case demonstrates the value of vismodegib treatment prior to surgery in a locally advanced, high-risk scalp BCC and highlights the importance of an individualized and specialized approach with these patients, within a multidisciplinary team.

Basal cell carcinoma: multimodal treatment and the role of neoadjuvant vismodegib.

Basal cell carcinoma (BCC) is the most common skin cancer. It generally has an indolent course with low rates of metastasis and mortality. However, BCC is locally invasive and can cause significant morbidity due to destructive local spread. We report our experience with a patient who was referred to our skin cancer unit due to a previously neglected lesion on the parietal region of the scalp, which had developed for 7 years. The patient was prescribed vismodegib on the basis that surgery could cause excessive functional and aesthetic damage. The patient had an objective partial response after 20 months of treatment. He was then submitted to radical skin excision, leaving a large defect that was reconstructed using a free latissimus dorsi muscle flap. The patient recovered well, and at the 1-year follow-up there were no signs of local recurrence. Our case demonstrates the value of vismodegib treatment prior to surgery in a locally advanced, high-risk scalp BCC and highlights the importance of an individualized and specialized approach with these patients, within a multidisciplinary team.

Primary malignant melanoma of the cervix: a rare disease.

Malignant melanoma (MM) arising primarily in the cervix is exceedingly rare and has a poor prognosis. We report the case of a primary MM of the cervix in a 64-year-old woman with vaginal bleeding. She presented with a cervical amelanotic lesion which on biopsy rendered the diagnosis of MM. The patient was staged as International Federation of Gynecology and Obstetrics IIB and underwent Wertheim-Meigshysterectomy followed by brachytherapy. One year later, she was diagnosed with a large pelvic relapse for which surgery was performed. She then presented with a vaginal relapse and an isolated hepatic lesion, both of which were proposed for surgery. The diagnosis of MM of the cervix is a clinical and pathological challenge due to its rarity and overlapping features. Cytology cannot accurately diagnose it. Moreover, amelanotic MMs must be distinguished from other poorly differentiated carcinomas by diagnosis that ultimately relies on immunohistochemical staining. Radical surgery is the only treatment showing predictive benefit.

Cervical cancer screening opportunities for Guinea-Bissau.

Guinea-Bissau is a severely resource constrained country, in search of political stability and development in every sector of public life. International aid is permanent and healthcare is one of the most targeted fields, focusing mostly on infectious diseases, maternity, infant malnutrition, access to healthcare and gender inequality in health. As in the rest of Sub-Saharan Africa, cervical cancer is gathering increasing attention from the community and ruling officers. The potential of screening for control of cervical cancer raised the interest of adapting screening methods to low-resource settings. This started the search for the best resource-adapted strategies, which promoted several trials that currently shape the development of screening programs in these countries. Prevention and control strategies are also being adapted taking into account the availability of human Papillomavirus vaccination. Nonetheless, several barriers are still in place for widespread vaccination programs, and cervical cancer screening and treatment remain central in the control of cervical cancer in low-resource settings. We intend to discuss current cervical cancer screening approaches in low-resource countries and opportunities for their implementation in Guinea-Bissau.