Transarterial (chemo)embolisation versus systemic chemotherapy for colorectal cancer liver metastases.

BACKGROUND: The liver is affected by two groups of malignant tumours: primary liver cancers and liver metastases. Liver metastases are significantly more common than primary liver cancer, and five-year survival after radical surgical treatment of liver metastases ranges from 28% to 50%, depending on primary cancer site. However, R0 resection (resection for cure) is not feasible in most people; therefore, other treatments have to be considered in the case of non-resectability. One possible option is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Transarterial chemoembolisation (TACE) of the peripheral branches of the hepatic artery can be achieved by administering a chemotherapeutic drug followed by vascular occlusive agents and can lead to selective necrosis of the cancer tissue while leaving normal liver parenchyma virtually unaffected. The entire procedure can be performed without infusion of chemotherapy and is then called bland transarterial embolisation (TAE). These procedures are usually applied over a few sessions. Another possible treatment option is systemic chemotherapy which, in the case of colorectal cancer metastases, is most commonly performed using FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) and FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) regimens applied in multiple sessions over a long period of time. These therapies disrupt the cell cycle, leading to death of rapidly dividing malignant cells. Current guidelines determine the role of TAE and TACE as non-curative treatment options applicable in people with liver-only or liver-dominant metastatic disease that is unresectable or non-ablatable, and in people who have failed systemic chemotherapy. Regarding the treatment modalities in people with colorectal cancer liver metastases, we found no systematic reviews comparing the efficacy of TAE or TACE versus systemic chemotherapy. OBJECTIVES: To evaluate the beneficial and harmful effects of transarterial embolisation (TAE) or transarterial chemoembolisation (TACE) compared with systemic chemotherapy in people with liver-dominant unresectable colorectal cancer liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and three additional databases up to 4 April 2024. We also searched two trials registers and the European Medicines Agency database and checked reference lists of retrieved publications. SELECTION CRITERIA: We included randomised clinical trials assessing beneficial and harmful effects of TAE or TACE versus systemic chemotherapy in adults (aged 18 years or older) with colorectal cancer liver metastases. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality; overall survival (time to mortality); and any adverse events or complications. Our secondary outcomes were cancer mortality; health-related quality of life; progression-free survival; proportion of participants dying or surviving with progression of the disease; time to progression of liver metastases; recurrence of liver metastases; and tumour response measures (complete response, partial response, stable disease, and progressive disease). For the purpose of the review and to perform necessary analyses, whenever possible, we converted survival rates to mortality rates, as this was our primary outcome. For the analysis of dichotomous outcomes, we used the risk ratio (RR); for continuous outcomes, we used the mean difference; and for time to event outcomes, we calculated hazard ratios (HRs), all with 95% confidence intervals (CI). We used the standardised mean difference with 95% CIs when the trials used different instruments. We used GRADE to assess the certainty of evidence for each outcome. We based our conclusions on outcomes analysed at the longest follow-up. MAIN RESULTS: We included three trials with 118 participants randomised to TACE versus 120 participants to systemic chemotherapy. Four participants were excluded; one due to disease progression prior to treatment and three due to decline in health. The trials reported data on one or more outcomes. Two trials were performed in China and one in Italy. The trials differed in terms of embolisation techniques and chemotherapeutic agents. Follow-up ranged from 12 months to 50 months. TACE may reduce mortality at longest follow-up (RR 0.86, 95% CI 0.79 to 0.94; 3 trials, 234 participants; very low-certainty evidence), but the evidence is very uncertain. TACE may have little to no effect on overall survival (time to mortality) (HR 0.61, 95% CI 0.37 to 1.01; 1 trial, 70 participants; very low-certainty evidence), any adverse events or complications (3 trials, 234 participants; very low-certainty evidence), health-related quality of life (2 trials, 154 participants; very low-certainty evidence), progression-free survival (1 trial, 70 participants; very low-certainty evidence), and tumour response measures (presented as the overall response rate) (RR 1.81, 95% CI 1.11 to 2.96; 3 trials, 234 participants; very low-certainty evidence), but the evidence is very uncertain. No trials reported cancer mortality, proportion of participants dying or surviving with progression of the disease, and recurrence of liver metastases. We found no trials comparing the effects of TAE versus systemic chemotherapy in people with colorectal cancer liver metastases. AUTHORS' CONCLUSIONS: The evidence regarding effectiveness of TACE versus systemic chemotherapy in people with colorectal cancer liver metastases is of very low certainty and is based on three trials. Our confidence in the results is limited due to the risk of bias, inconsistency, indirectness, and imprecision. It is very uncertain whether TACE confers benefits with regard to reduction in mortality, overall survival (time to mortality), reduction in adverse events or complications, improvement in health-related quality of life, improvement in progression-free survival, and tumour response measures (presented as the overall response rate). Data on cancer mortality, proportion of participants dying or surviving with progression of the disease, and recurrence of liver metastases are lacking. We found no trials assessing TAE versus systemic chemotherapy. More randomised clinical trials are needed to strengthen the body of evidence and provide insight into the benefits and harms of TACE or TAE in comparison with systemic chemotherapy in people with liver metastases from colorectal cancer.

Dermoscopy of Chronic Radiation-Induced Dermatitis in Patients with Head and Neck Cancers Treated with Radiotherapy.

Radiotherapy (RT) is an integral part of many cancer treatment protocols. Chronic radiation-induced dermatitis (CRD) is a cutaneous toxicity that occurs in one-third of all patients treated with this method. CRD is usually observed several months after completion of treatment. Typical symptoms of CRD are telangiectasia, skin discoloration, atrophy, thickening, and cutaneous fibrosis. There are currently no data in the literature on the evaluation of the dermoscopic features of CRD. The aim of this prospective study was the identification of clinical and dermoscopic features in a group of 32 patients with head and neck cancer (HNC) in whom CRD developed after RT. CRD was assessed at 3, 6, and 12 months after RT in 16, 10, and 10 patients, respectively. CRD was assessed at one time point and two time points in 28 and 4 patients, respectively. The control included skin areas of the same patient not exposed to RT. The dataset consisted of 36 clinical and 216 dermoscopic photos. Clinical evaluation was performed according to the RTOG/EORTC radiation-induced dermatitis scale. The highest score was grade 2 observed in 21 patients. Clinical observations revealed the presence of slight and patchy atrophy, pigmentation change, moderate telangiectasias, and some and total hair loss. Dotted vessels, clustered vessel distribution, white patchy scale, perifollicular white color, white structureless areas, brown dots and globules, and white lines were the most frequently noted features in dermoscopy. Three independent risk factors for chronic toxicity, such as age, gender, and surgery before RT, were identified. The dermoscopic features that had been shown in our study reflect the biological reaction of the skin towards radiation and may be used for the parametrization of CRD regarding its intensity and any other clinical consequences in the future.

Dermoscopy of acute radiation-induced dermatitis in patients with head and neck cancers treated with radiotherapy.

Head and neck cancer (HNC) was the seventh most common cancer in the world in 2018. Treatment of a patient may include surgery, radiotherapy (RT), chemotherapy, targeted therapy, immunotherapy, or a combination of these methods. Ionizing radiation used during RT covers relatively large volumes of healthy tissue surrounding the tumor. The acute form of radiation-induced dermatitis (ARD) are skin lesions that appear usually within 90 days of the start of RT. This is a prospective study which compares 2244 dermoscopy images and 374 clinical photographs of irradiated skin and healthy skin of 26 patients at on average 15 time points. Dermoscopy pictures were evaluated independently by 2 blinded physicians. Vessels in reticular distribution, white, yellow or brown scale in a patchy distribution, perifollicular pigmentation and follicular plugs arranged in rosettes were most often observed. For these dermoscopic features, agreement with macroscopic features was observed. Two independent predictors of severe acute toxicity were identified: gender and concurrent chemotherapy. Knowledge of dermoscopic features could help in the early assessment of acute toxicity and the immediate implementation of appropriate therapeutic strategies. This may increase the tolerance of RT in these groups of patients.

What Do the Lips Say in Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation? A Case Series.

INTRODUCTION: Chronic graft-versus-host disease (cGvHD) affects around half of allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients, with frequent involvement of the oral mucosa and lip vermillion, that clinically may resemble other autoimmune and inflammatory conditions. Our objectives were to define the dermoscopic patterns of lip vermilion in patients suffering from cGvHD and to compare the presentation with previously published dermoscopic presentations of other disease entities presenting on the lip vermillion. METHODS: A group of 16 patients diagnosed with cGvHD was assessed clinically and dermoscopically. The dermoscopic descriptions were made according to recent consensus on terminology of non-neoplastic disorders. RESULTS: Dermoscopy of vermillion frequently revealed dotted vessels that were found in all patients, while linear vessels without bends or branches were seen in 10 of them (62.5%). Peripheral scale, mainly in white color (13/16, 81.2%) was often present. Most striking features were parallel and perpendicular white lines, found in all patients. Other structures included brown dots and blood spots that were present in 10 patients (62.5%). Four patients (25.0%) had blurred vermillion border and in 8 (50.0%) linear fissures or ulceration were found. Typical Wickham striae were found in 3 (18.8%) patients. CONCLUSIONS: The dermoscopic features observed in cGvHD affecting lip vermillion warrant differentiation with inflammatory (lichen planus), autoimmune (lichen sclerosus, discoid lupus erythematosus), precancerous (actinic keratosis, leukoplakia), and neoplastic diseases (squamous cell carcinoma), among others. Dermoscopy of lip vermillion might be an additional tool to visualize diagnostic mucoscopic features of cGvHD (lichen planus-like, lichen sclerosus-like lesions).

Secondary skin neoplasms in patients after autologous and allogeneic hematopoietic stem cell transplantation procedures.

The increasing number of hematopoietic stem cell transplantation (HSCT) procedures and lower transplant-related mortality has led to a growing population of survivors facing long-term increased risk of secondary malignancy, including cutaneous neoplasms. In this review, we aim to discuss the incidence, risk factors and preventive strategies for secondary skin neoplasms after autologous and allogeneic HSCT. Cutaneous neoplasms, such as basal cell carcinoma, squamous cell carcinoma and melanoma, are among the most common solid cancers arising in patients after HSCT. Besides risk factors established in the general population, primary disease, chronic graft-versus-host disease (CGvHD), prolonged immunosuppression, especially with the use of cyclosporine and azathioprine, radiation exposure, light skin color, male sex, and young age at transplantation play a role in the development of cutaneous neoplasms in HSCT recipients. Skin cancer development after HSCT may be explained by cumulative effects of chemotherapy and radiotherapy-induced DNA damage, prolonged immunosuppressive conditions and chronic mucosal inflammation, particularly after allogeneic HSCT. Delayed immune recovery and persistent immunodeficiency in patients with graft-versus-host disease (GvHD) may also contribute to carcinogenesis. Regular dermatological surveillance and prompt recognition of precancerous and cancerous lesions is crucial for patient's prognosis and management.

Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma: A Case Report.

We present a case of a young patient with life-threatening pulmonary complications after allogeneic hematopoietic stem cell transplantation (HSCT). The 25-year-old woman, after HSCT for multiple myeloma, developed severe chronic graft-vs-host disease (GvHD), including bronchiolitis obliterans syndrome. During the treatment of chronic GvHD, 18 months after HSCT, she experienced sudden massive pulmonary hemorrhage with cardiac arrest. The computed tomography imaging revealed lesions suggestive of fungal etiology, with cavity adjacent to the pulmonary vessels. Disqualified from invasive treatment due to poor pulmonary performance, she was treated conservatively with broad-spectrum antibiotics and antifungals. The microbiological workup consistently revealed only Pseudomonas aeruginosa colonization. Her condition steadily improved on treatment. Over 18 months after the incident, she did not experience recurrent bleeding nor serious infection, her primary disease remains in remission, and GvHD symptoms are controlled. Allogeneic HSCT offers possibility of sustained immune-mediated disease control and sometimes even cure, but despite reduced transplant related mortality, GvHD and infections may be detrimental for transplant recipients. Our report illustrates atypical manifestation of pulmonary lesions and highlights the importance of infection control during GvHD treatment.