Unleashing the potential: transarterial chemoembolization combined with intra-arterial infusion of bevacizumab for unresectable hepatocellular carcinoma.

BACKGROUND: The purpose of this study is to compare the efficacy and safety of transarterial chemoembolization (TACE) alone with transarterial chemoembolization combined with the arterial infusion of bevacizumab (TACE + Bev) in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: A retrospective analysis was conducted on 446 uHCC patients treated with TACE or TACE + Bev between January 2021 and March 2023. The study evaluated objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events in both treatment groups. RESULTS: Finally, the TACE group comprised 295 patients, and the TACE + Bev group comprised 151 patients. Patients in the TACE + Bev group exhibited significantly prolonged median PFS (7.9 months vs. 10.3 months, P = 0.013) and median OS (16.1 months vs. 21.4 months, P = 0.041), improved ORR (26.8% vs. 37.7%, P = 0.017) and DCR (71.5% vs. 80.8%, P = 0.033) compared to the TACE group. Multifactorial Cox analysis identified alpha-fetoprotein (AFP) > 400 ng/ml as an independent prognostic factor for PFS and OS. Meanwhile, portal vein cancer thrombosis and distant metastasis are poor prognostic factors for OS. The overall incidence of adverse events was similar between the two groups. CONCLUSION: In comparison with the TACE group, the TACE + Bev group demonstrated efficacy in improving outcomes for patients with uHCC with a manageable safety profile.

Intraoperative radiofrequency ablation for unresectable abdominal paraganglioma: a case report.

For pheochromocytoma and paraganglioma (PPGL), the efficacy of percutaneous ablative therapies in achieving control of metastatic tumors measuring <3 cm had been demonstrated in only few reports, and intraoperative radiofrequency ablation (RFA) of locally invasive primary PPGLs has not been reported. We presented the case of a 31-year-old man who had a 9-cm functioning unresectable PPGL. He was treated with 13 cycles of cytotoxic chemotherapy without objective tumor response, according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, magnetic resonance imaging revealed a 9.0 × 8.6 × 6.0-cm retroperitoneal mass that extended to the inferior portion of the inferior vena cava, the inferior mesenteric artery, and the infrarenal aorta. Biochemical evaluation demonstrated high level of plasma normetanephrine (20.2 nmol/L, normal range <0.9 nmol/L). Genetic investigation showed the germline pathogenic variant c.1591delC (p. Ser198Alafs*22) in the SDHB gene. I131-metaiodobenzylguanidine scintigraphy was negative and Ga68-dotatate PET-CT scan showed high tumor uptake without distant metastases. On open laparotomy, tumor debulking was not possible. Therefore, intraoperative RFA was performed by a highly experienced team of interventional radiologists. At 12 months after the RFA, the tumor volume decreased from 208 to 45 mL (78%), plasma normetanephrine decreased from 20.2 to 2.6 nmol/L (87%), and the doxazosin dose was reduced from 16 to 8 mg/day. To our best knowledge, this was the first report on intraoperative RFA that markedly reduced the size of a large primary unresectable PPGL, along with clinical and biochemical responses.

Actual over 3-year survival after stereotactic body radiation therapy in patients with unresectable intrahepatic cholangiocarcinoma.

PURPOSE: As a non-invasive treatment, stereotactic body radiation therapy (SBRT) has been an emerging and effective option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). The Cyber Knife has an SBRT system, which can realize real-time tracking of tumors during treatment. It can protect the surrounding normal liver tissue while the tumor gets the therapeutic dose. The purpose of this study was to evaluate the factors affecting the local control rate for patients after SBRT treatment, and to predict the factors affecting survival rates, then to report the 3-year actual survival rates after treatment and identify the influencing factors of 3-year survival rate. MATERIALS AND METHODS: We conducted a long-term follow-up of 43 patients with unresectable intrahepatic cholangiocarcinoma who underwent Cyber Knife in our hospital from January 2016 to December 2018. Regular medical check-ups were performed every 2-3 months after SBRT to evaluated the effect of treatment. RESULTS: The median follow-up time was 15 months (4-78 months), and the median progression-free survival (PFS) was 6 months (95% CI, 2.788-9.212) and the median overall survival (OS) was 12 months (95% CI, 3.434-20.566), respectively. Based on modified Response Evaluation and Criteria in Solid Tumor (mRECIST), response rate (RR) and disease control rate (DCR) of SBRT in unresectable ICC were 55.2% and 86%. The 1-, 2- and 3-years OS rate were 51.2%, 32.6% and 23.3%. Multivariate analysis based on competing risk survival analysis identified that patients with multiple nodules, large diameter, high level of CA199 and CEA, poor ECOG performance status had worse overall survival (p < 0.05). Patients who survived ≥3 years had significantly lower levels of CEA, CA199, smaller tumor diameters and lower number of lesions (p < 0.05). CONCLUSION: The SBRT might be a candidate option for patients who unable to perform surgery. The rate of 3-year survival after SBRT for unresectable ICC can be expected with 23.3%.

Therapeutic Options in Unresectable Oral Squamous Cell Carcinoma: A Systematic Review.

PURPOSE: This review describes the current scientific evidence of therapeutic options in unresectable oral squamous cell carcinoma. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched MEDLINE (Via PubMed) to identify studies assessing treatments for unresectable oral squamous cell carcinoma. The methodological quality assessment of the included studies was performed using the Joanna Briggs Institute (JBI) checklist tool. The evidence was organized and presented using tables and narrative synthesis. RESULTS: Thirty-three studies met the eligibility criteria. Most studies had an observational design. The sample size varied from 16 to 916 participants. The methodology quality of the included studies ranged from 2.5 to 10 using the JBI tool. Overall, the optimal treatment of patients with unresectable oral cancer is challenging, so there is a sprinkling of studies assessing a variety of therapeutic options, such as radiotherapy, chemotherapy, concurrent chemoradiotherapy, immunotherapy, targeted therapy plus chemotherapy or radiotherapy, and gene therapy plus chemotherapy. CONCLUSION: There is lacking evidence about the benefits of some therapeutic options for unresectable oral squamous cell carcinoma. Overall, these patients can be treated using a multimodal approach such as concurrent chemoradiotherapy or induction chemotherapy followed by chemoradiotherapy, which have shown good clinical outcomes. However, other options could be considered depending on the assessment of risk/benefits, tumor extension, and patient values and preferences.

Long-term outcomes of induction chemotherapy followed by chemoradiotherapy vs chemoradiotherapy alone as treatment of unresectable head and neck cancer: follow-up of the Spanish Head and Neck Cancer Group (TTCC) 2503 Trial.

BACKGROUND: Our previous phase-3 study (TTCC 2503) failed to show overall survival advantage of 2 induction chemotherapy (IC) regimens followed by standard concurrent chemoradiotherapy (CRT) over CRT alone in patients with unresectable locally advanced head and neck squamous-cell carcinoma (LAHNSCC). This study described the long-term survival of those patients. MATERIALS AND METHODS: Long-term follow-up study of patients with untreated LAHNSCC assigned to IC (three cycles), with either docetaxel, cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CRT, or CRT alone, included in the previous TTCC 2503 trial. RESULTS: In the intention-to-treat population (n = 439), the median OS times were 25.4 (95% CI, 16.8-34.4), 26.2 (95% CI, 18.2-36.6) and 25.4 months (95% CI, 17.4-36.0) in the TPF-CRT, PF-CRT and CRT arms, respectively (log-rank p = 0.51). In the per-protocol population (n = 355), patients with larynx-hypopharynx primary tumors treated with IC (TPF or PF) followed by CRT had a longer median PFS than those who received CRT alone. Moreover, patients with ECOG 0 treated with IC (TPF or PF) followed by CRT had a better TTF than those with CRT alone. There were no statistically significant differences in terms of OS, PFS or TTF, according to the tumor load or affected nodes. CONCLUSION: After a long follow-up, the TTCC 2503 trial failed to show the benefit of IC-CRT in unresectable LAHNSCC regarding the primary end point. However, fit patients with ECOG 0 and primary larynx-hypopharyngeal tumors may benefit from the use of IC if administered by an experienced team. ClinicalTrials.gov identifier NCT00261703.

Sorafenib treatment by Child-Pugh score in Latin American patients with hepatocellular carcinoma.

Aim: To evaluate sorafenib treatment in Latin American patients with unresectable hepatocellular carcinoma in the real-world GIDEON study. Patients & methods: Sorafenib administration, safety and efficacy were analyzed by Child-Pugh status. Results: Of 90 evaluable patients (37% Child-Pugh A, 46% Child-Pugh B and 3% Child-Pugh C at study entry), 97% started sorafenib at 800 mg/day. Patients with Child-Pugh B7 had the longest median treatment duration of sorafenib (33.1 weeks). Sorafenib-related adverse events occurred in 58% of patients with Child-Pugh A (21% grade 3/4) and 46% with Child-Pugh B (7% grade 3/4). Conclusion: Sorafenib had a similar safety profile across patients with Child-Pugh A and B and is a treatment option for both groups.

Chemo-radiotherapy integration in unresectable locally advanced non-small-cell lung cancer: a review.

Approximately one-third of all non-small-cell lung cancer (NSCLC) are locally-advanced at diagnosis, and 15-17% of these tumors are unresectable at presentation. Definitive chemo-radiotherapy (CRT) represents the standard therapeutic approach. However, the literature has shown that only 15% of patients are alive at 5 years and this percentage has remained unchanged despite various attempts of improvement. The recent introduction of immunotherapy has not only strongly changed the clinical scenario but has also drawn attention to a stage of disease apparently forgotten for decades. Stage III NSCLC can represent an interesting setting for the combined use of chemo-radiation and immunotherapy, due to the potential synergistic effect between radiation and immune checkpoint inhibitors. We reviewed the available literature in order to report the state of art of stage III NSCLC, by focusing on trials that evaluate different combinations of CRT and new drugs of PD-1/PD-L1 axis, and anti-CTLA-4. The future goal in the management of unresectable stage III NSCLC will be the optimal patients' selection combined with the use of individualized immuno/chemotherapies that could potentially improve clinical outcomes.

Neoadjuvant Multikinase Inhibitor in Patients With Locally Advanced Unresectable Thyroid Carcinoma.

Background: Papillary thyroid carcinoma (PTC) is the most common and less aggressive thyroid cancer, but some patients may display locally advanced disease. Therapeutic options are limited in these cases, particularly for those patients with unresectable tumors. Neoadjuvant therapy is not part of the recommended work up. Methods: Report a case of an unresectable grossly locally invasive PTC successfully managed with neoadjuvant therapy and provide a systematic review (SR) using the terms "Neoadjuvant therapy" AND "Thyroid carcinoma." Results: A 32-year-old man with a 7.8 cm (in the largest dimension) PTC was referred to total thyroidectomy, but tumor resection was not feasible due to extensive local invasion (trachea, esophagus, and adjacent structures). Sorafenib, a multikinase inhibitor (MKI), was initiated; a 70% tumor reduction was observed after 6 months, allowing new surgical intervention and complete resection. Radioactive iodine (RAI) was administered as adjuvant therapy, and whole body scan (WBS) shows uptake on thyroid bed. One-year post-surgery the patient is asymptomatic with a status of disease defined as an incomplete biochemical response. The SR retrieved 123 studies on neoadjuvant therapy use in thyroid carcinoma; of them, 6 were extracted: 4 case reports and 2 observational studies. MKIs were used as neoadjuvant therapy in three clinical cases with 70-84% of tumor reduction allowing surgery. Conclusion: Our findings, along with other reports, suggest that MKIs is an effective neoadjuvant therapy and should be considered as a therapeutic strategy for unresectable grossly locally invasive thyroid carcinomas.

Treatment Patterns Among Patients with Metastatic and/or Unresectable Gastric Cancer in Brazil.

PURPOSE: In Brazil, patients with gastric cancer have not been systematically followed-up and evaluated, thus data regarding patterns of care and outcomes are scarce or missing. The objective of this study was to evaluate patterns of care of advanced gastric cancer in standard practice in Brazil. METHODS: This was an observational, multicenter, retrospective study, which included patients with metastatic and/or unresectable gastric cancer (MGC) who underwent at least one line of treatment. RESULTS: We analyzed data on 155 patients diagnosed with MGC, most are men (57.4%), with mean age of 61.9 years at diagnosis, with 99 (63.9%) from the public healthcare system and 56 (36.1%) from the private setting. Platinum- and/or fluoropyrimidine-containing regimens prevailed as first-line therapy, while irinotecan was the most used regimen in the second and in the third lines. More than 40% of patients underwent only one line of systemic therapy, of which around 40% either died during the treatment or went on to best supportive care (BSC) only. The remaining patients received further treatment lines. A fifth of the patients in the study died within two months after discontinuation of the first-line treatment. Adverse events, use of concomitant medications, support procedures, outpatient visits, and hospitalizations were reported for most patients, especially in the first and second lines of treatment and during exclusive BSC. CONCLUSIONS: Survival during or after the first-line chemotherapy remains poor among patients with MGC. Adverse events and health resource use were common in the first and second lines of treatment and in exclusive BSC. These results suggest that there is space for improvement in the treatment of MGC in Brazil.

Management of unresectable, locally advanced pancreatic adenocarcinoma.

The diagnosis of unresectable locally advanced pancreatic adenocarcinoma (LAPC) requires confirmation, through imaging tests, of the unfeasibility of achieving a complete surgical resection, in the absence of metastatic spread. The increase in overall survival (OS), together with an appropriate symptom management is the therapeutic target in LAPC, maintaining an acceptable quality of life and, if possible, increasing the time until the appearance of metastasis. Chemoradiation (CRT) improves OS compared to best support treatment or radiotherapy (RT) but with greater toxicity. No significant increase in OS has been achieved with CRT when compared to chemotherapy (QT) alone in patients without disease progression after four months of treatment with QT. However, a significantly better local control, that is, a significant increase in the time to disease progression was associated with this approach. The greater effectiveness of the schemes FOLFIRINOX and gemcitabine (Gem) + Nab-paclitaxel compared to gemcitabine alone, has been extrapolated from metastatic disease to LAPC, representing a possible alternative for patients with good performance status (ECOG 0-1). In the absence of randomized clinical trials, Gem is the standard treatment in LAPC. If disease control is achieved after 4-6 cycles of QT, the use of CRT for consolidation can be considered an option vs QT treatment maintenance. Capecitabine has a better toxicity profile and effectiveness compared to gemcitabine as a radiosensitizer. After local progression, and without evidence of metastases, treatment with RT or CRT, in selected patients, can support to maintain the regional disease control.

[Partial stomach partitioning gastrojejunostomy in the treatment of the malignant gastric outlet obstruction]. / Gastro yeyuno anastomosis con separación gástrica parcial en el tratamiento de la obstrucción gastroduodenal secundaria a cáncer gástrico avanzado.

BACKGROUND: In patients with unresectable gastric cancer and outlet obstruction syndrome, gastric partitioning gastrojejunostomy is an alternative, which could avoid the drawbacks of the standard techniques. OBJECTIVE: Comparison of antroduodenal stent, conventional gastrojejunostomy and gastric partitioning gastrojejunostomy. MATERIAL AND METHODS: A retrospective, cross-sectional study was conducted on patients with unresectable distal gastric cancer and gastric outlet obstruction, treated with the three different techniques over the last 12 years, comparing results based on oral tolerance and complications. An analysis was performed on the results using the Student-t test for independent variables. RESULTS: The 22 patients were divided in 3 groups: group I (6 cases) stent, group II (9 cases) conventional gastrojejunostomy, and group III (7 cases) gastric partitioning gastrojejunostomy, respectively. The stent allows a shorter "postoperative" stay and early onset of oral tolerance (P<0.05), however, the gastric partitioning gastrojejunostomy achieve normal diet at 15th day (P<0.05). The mortality rate was higher in the stent group (33%) compared with surgical techniques, with a morbidity of 4/6 (66.7%) in Group I, 6/9 (66.7%) Group II, and 3/7 (42%) Group III. Re-interventions: 2/6 Group I, 3/9 Group II, and 0/7 Group III. The median survival was superior in the gastric partitioning gastrojejunostomy, achieving an overall survival of 6.5 months. CONCLUSIONS: The gastric partitioning gastrojejunostomy for treatment of gastric outlet obstruction in unresectable advanced gastric cancer is a safe technique, allowing a more complete diet with lower morbidity and improved survival.