ABSTRACT
BACKGROUND: The 9th edition of the lung cancer tumor-node-metastasis (TNM) staging introduced adjustments, including the reclassification of T1N1M0 patients from stage IIB to IIA. This update used data mostly from Asian populations. However, the applicability of these adjustments to Caucasian patients remains uncertain. METHODS: Stage II non-small cell lung cancer (NSCLC) patients from the Surveillance, Epidemiology, and End Results (SEER) database were included. Kaplan-Meier analysis with log-rank testing compared overall survival (OS) and cancer-specific survival (CSS). Propensity score matching (PSM) balanced baseline characteristics. The least absolute shrinkage and selection operator (LASSO)-based Cox analyses identified prognostic factors. RESULTS: Among 10,470 eligible stage II NSCLC patients (median age: 69 years; male: 53.1%), there were 2736 in stage IIA, 2112 in IIA New, and 5622 in IIB groups. Before PSM, survival outcomes of stage IIA New patients were similar to those of stage IIA patients but better than those of stage IIB. After PSM, stage IIA New and IIB patients showed similar survival rates (OS, p = 0.276; CSS, p = 0.565). Conversely, stage IIA New patients had worse outcomes than stage IIA patients (OS, p < 0.001; CSS, p = 0.005). LASSO-based Cox analyses confirmed stage IIA New patients had inferior prognosis compared to stage IIA patients (OS HR: 1 vs. 1.325, p < 0.001; CSS HR: 1 vs. 1.327, p < 0.001). CONCLUSIONS: The downstaging of T1N1M0 patients from stage IIB to IIA in the 9th edition TNM staging remains unverified in Caucasians. Caution is warranted in assessing the staging and prognosis of these individuals. Further validation of our findings is necessary.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Neoplasm Staging , SEER Program , White People , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Male , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Female , Aged , Middle Aged , Lymphatic Metastasis , Prognosis , Kaplan-Meier Estimate , Propensity ScoreABSTRACT
OPINION STATEMENT: Liver transplantation for hepatocellular carcinoma (HCC) remains an evolving field. Major challenges HCC transplant patients face today include liver organ donor shortages and the need for both better pre-transplant bridging/downstaging therapies and post-transplant HCC recurrence treatment options. The advent of immunotherapy and the demonstrated efficacy of immune checkpoint inhibitors in multiple solid tumors including advanced/unresectable HCC hold promise in expanding both the neoadjuvant and adjuvant HCC transplant treatment regimen, though caution is needed with these immune modulating agents leading up to and following transplant. New options for pre-transplant HCC management will expand access to this curative option as well as ensure patients have adequate control of their HCC prior to transplant to maximize the utility of a liver donor. Machine perfusion has been an active area of investigation in recent years and could expand the organ donor pool, helping address current liver donor shortages. Finally, additional HCC biomarkers such as AFP-L3 and DCP have shown promise in improving risk stratification of HCC patients. Together, these three recent advancements will likely alter HCC transplant guidelines in the coming years.
ABSTRACT
Immunotherapy has revolutionised the treatment of advanced hepatocellular carcinoma (HCC). In addition, several phase III trials of immunotherapy in combination with surgical or locoregional therapies for early-to intermediate-stage HCC have recently reported positive results, and other phase III trials in the same patient population are currently in progress. As the application of immunotherapy is shifting to include patients with earlier stages of HCC, one looming question now emerges: What is the role of immunotherapy in the pre-liver transplant population? Liver transplantation is a potentially curative therapy for HCC and confers the additional advantage of restoring a normal, healthy liver. In pre-transplant patients, immunotherapy may improve downstaging success and tumour control at the cost of some immunologic risks. These include immune-related toxicities, which are particularly relevant in a uniquely vulnerable population with chronic liver disease, and the possibility of acute rejection after transplantation. Ultimately, the goal of immunotherapy in this population will be to effectively expand access to liver transplantation while preserving pre- and post-transplant outcomes. In this review, we discuss the mechanisms supporting combination immunotherapy, summarise key recent clinical data from major immunotherapy trials, and explore how immunotherapy can be applied in the neoadjuvant setting prior to liver transplantation in selected high-risk patients.
ABSTRACT
A significant number of patients with hepatocellular carcinoma (HCC) are usually diagnosed in advanced stages, that leads to inability to achieve cure. Palliative options are focusing on downstaging a locally advanced disease. It is well-supported in the literature that patients with HCC who undergo successful conversion therapy followed by curative-intent surgery may achieve a significant survival benefit compared to those who receive chemotherapy alone or those who are successfully downstaged with conversion therapy but not treated with surgery. Hepatic artery infusion chemotherapy can be a potential downstaging strategy, since recent studies have demonstrated excellent outcomes in patients with colorectal liver metastatic disease as well as primary liver malignancies.
Subject(s)
Carcinoma, Hepatocellular , Infusions, Intra-Arterial , Liver Neoplasms , Neoplasm Staging , Humans , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/mortality , Treatment Outcome , Hepatic Artery , Hepatectomy , Palliative Care/methodsABSTRACT
Efforts on bladder cancer treatment have been shifting from extensive surgery to organ preservation in the past decade. To this end, we herein develop a multifunctional nanoagent for bladder cancer downstaging and bladder-preserving therapy by integrating mucosa penetration, reduced off-target effects, and internal irradiation therapy into a nanodrug. Specifically, an iron oxide nanoparticle was used as a carrier that was coated with hyaluronic acid (HA) for facilitating mucosa penetration. Dibenzocyclooctyne (DBCO) was introduced into the HA coating layer to react through bioorthogonal reaction with azide as an artificial receptor of bladder cancer cells, to improve the cellular internalization of the nanoprobe labeled with 177Lu. Through magnetic resonance imaging, the targeted imaging of both nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) was realized after intravesical instillation of the multifunctional probe, both NMIBC and MIBC were found downstaged, and the metastasis was inhibited, which demonstrates the potential of the multifunctional nanoprobe for bladder preservation in bladder cancer treatment.
Subject(s)
Lutetium , Radioisotopes , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/pathology , Humans , Lutetium/chemistry , Radioisotopes/chemistry , Animals , Cell Line, Tumor , Magnetic Resonance Imaging , Mice , Hyaluronic Acid/chemistryABSTRACT
BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) combined with portal and hepatic vein cancerous thrombosis is poor, for unresectable patients the combination of targeted therapy and immune therapy was the first-line recommended treatment for advanced HCC, with a median survival time of only about 2.7-6 months. In this case report, we present the case of a patient with portal and hepatic vein cancerous thrombosis who achieved pathologic complete response after conversion therapy. CASE SUMMARY: In our center, a patient with giant HCC combined with portal vein tumor thrombus and hepatic vein tumor thrombus was treated with transcatheter arterial chemoembolization (TACE), radiotherapy, targeted therapy and immunotherapy, and was continuously given icaritin soft capsules for oral regulation. After 7 months of conversion therapy, the patient's tumor shrank and the tumor thrombus subsided significantly. The pathology of surgical resection was in complete remission, and there was no progression in the postoperative follow-up for 7 months, which provided a basis for the future strategy of combined conversion therapy. CONCLUSION: In this case, atezolizumab, bevacizumab, icaritin soft capsules combined with radiotherapy and TACE had a good effect. For patients with hepatocellular carcinoma combined with hepatic vein/inferior vena cava tumor thrombus, adopting a high-intensity, multimodal proactive strategy under the guidance of multidisciplinary team (MDT) is an important attempt to break through the current treatment dilemma.
ABSTRACT
Background and Objectives: Cervical cancer is the fourth most frequent type of neoplasia in women. It is most commonly caused by the persistent infection with high-risk strands of human papillomavirus (hrHPV). Its incidence increases rapidly from age 25 when routine HPV screening starts and then decreases at the age of 45. This reflects both the diagnosis of prevalent cases at first-time screening and the likely peak of HPV exposure in early adulthood. For early stages, the treatment offers the possibility of fertility preservation.. However, in more advanced stages, the treatment is restricted to concomitant chemo-radiotherapy, combined, in very selected cases with surgical intervention. After the neoadjuvant treatment, an imagistic re-evaluation of the patients is carried out to analyze if the stage of the disease remained the same or suffered a downstaging. Lymph node downstaging following neoadjuvant treatment is regarded as an indubitable prognostic factor for predicting disease recurrence and survival in patients with advanced cervical cancer. This study aims to ascertain the important survival role of radiotherapy in the downstaging of the disease and of lymphadenectomy in the control of lymph node invasion for patients with advanced-stage cervical cancer. Material and Methods: We describe the outcome of patients with cervical cancer in stage IIIC1 FIGO treated at Bucharest Oncological Institute. All patients received radiotherapy and two-thirds received concomitant chemotherapy. A surgical intervention consisting of type C radical hysterectomy with radical pelvic lymphadenectomy was performed six to eight weeks after the end of the neoadjuvant treatment. Results: The McNemar test demonstrated the regression of lymphadenopathies after neoadjuvant treatment-p: <0.001. However, the persistence of adenopathies was not related to the dose of irradiation (p: 0.61), the number of sessions of radiotherapy (p: 0.80), or the chemotherapy (p: 0.44). Also, there were no significant differences between the adenopathies reported by imagistic methods and those identified during surgical intervention-p: 0.62. The overall survival evaluated using Kaplan-Meier curves is dependent on the post-radiotherapy FIGO stage-p: 0.002 and on the lymph node status evaluated during surgical intervention-p: 0.04. The risk factors associated with an increased risk of death were represented by a low preoperative hemoglobin level (p: 0.003) and by the advanced FIGO stage determined during surgical intervention (p-value: 0.006 for stage IIIA and 0.01 for stage IIIC1). In the multivariate Cox model, the independent predictor of survival was the preoperative hemoglobin level (p: 0.004, HR 0.535, CI: 0.347 to 0.823). Out of a total of 33 patients with neoadjuvant treatment, 22 survived until the end of the study, all 33 responded to the treatment in varying degrees, but in 3 of them, tumor cells were found in the lymph nodes during the intraoperative histopathological examination. Conclusions: For advanced cervical cancer patients, radical surgery after neoadjuvant treatment may be associated with a better survival rate. Further research is needed to identify all the causes that lead to the persistence of adenopathies in certain patients, to decrease the FIGO stage after surgical intervention, and, therefore, to lower the risk of death. Also, it is mandatory to correctly evaluate and treat the anemia, as it seems to be an independent predictor factor for mortality.
Subject(s)
Neoadjuvant Therapy , Neoplasm Staging , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/mortality , Neoadjuvant Therapy/methods , Adult , Middle Aged , Lymph Node Excision , Lymph Nodes/pathology , Hysterectomy , Lymphatic Metastasis , AgedABSTRACT
Background/aims: Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC (uHCC) for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezobev remains unknown. Methods: In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging. Results: Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age: 58.5 years; women-17%; Barcelona Clinic Liver Cancer Stage System B/C:5/7) had received 3-12 cycles of atezo-bev, and 4 of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 (54-114) days following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 (4-30) months, none of the alive patients developed HCC recurrence or graft rejection. Conclusions: Surgical therapy, including LT, is possible after atezo-bev therapy in wellselected patients after downstaging.
ABSTRACT
Purpose: The aim of this retrospective analysis was to determine if the response to preoperative radio(chemo)therapy is predictive for survival among patients with locally advanced rectal cancer and may act as a potential surrogate endpoint for disease free survival and overall survival. Results: Eight hundred seventy-eight patients from five centers were analyzed. There were 304 women and 574 men; the median age was 64.7 years. 77.6% and 22.4% of patients received neoadjuvant radiochemotherapy or short-course radiotherapy, resulting in a pathological complete response in 7.3%. T-downstaging and N-downstaging occurred in 50.5% and 37% of patients after neoadjuvant therapy. In patients with T-downstaging, the 10-year DFS and 10-year OS were 64.8% and 66.8% compared to 37.1% and 45.9% in patients without T-downstaging. N-downstaging resulted in 10-year DFS and 10-year OS in 56.2% and 62.5% compared to 47.3% and 52.3% without N-downstaging. Based on routinely evaluated clinical parameters, an absolute risk prediction calculator was generated for 5-year disease-free survival, and 5-year overall survival. Conclusion: T-downstaging and N-downstaging after neoadjuvant radiochemotherapy or short-course radiotherapy resulted in better DFS and OS compared to patients without response. Based on clinical parameters, 5-year DFS, and 5-year OS can be predicted using a prediction calculator.
ABSTRACT
For patients with operable breast cancer, neoadjuvant systemic therapy (NST) can be used to downstage the primary tumor in the breast and to facilitate breast-conserving surgery (BCS) in patients with large tumors who desire breast conservation. Rates of breast pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) are highest in patients with triple-negative and human epidermal growth factor receptor 2 (HER2) positive (HER2+) disease; however, achieving pCR is not necessary for successful downstaging and avoidance of mastectomy, and rates of conversion to BCS-eligibility are high across all receptor subtypes. Neoadjuvant endocrine therapy (NET) can be used instead of NAC in postmenopausal patients with hormone receptor positive (HR+)/HER2 negative (HER2-) breast cancer to downstage the breast, particularly when the patient has no clear indication for systemic chemotherapy, but desires breast conservation. In patients treated with NET, rates of conversion to BCS-eligibility are similar to rates observed with NAC. The oncologic safety of BCS after NAC and NET has been established in prospective trials, and local recurrence (LR) rates are acceptably low provided negative surgical margins can be obtained. Investigation is under way to determine the feasibility and safety of omitting breast surgery in patients with responsive subtypes who have no residual invasive or in situ disease identified on post-treatment tumor bed biopsies; however, the significant risk of missing residual disease-which may impact selection of adjuvant systemic therapy-may preclude future adoption of this approach.
ABSTRACT
BACKGROUND: Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial. AIM: To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future. METHODS: We conducted a survey of major centers in India that performed LT in December 2022. A total of 23 responses were received. The centers were classified as high- and low-volume, and the current trend of care for patients und ergoing LT for HCC was noted. RESULTS: Of the 23 centers, 35% were high volume center (> 500 Liver transplants) while 52% were high-volume centers that performed more than 50 transplants/year. Approximately 39% of centers had performed > 50 LT for HCC while the percent distribution for HCC in LT patients was 5%-15% in approximately 73% of the patients. Barring a few, most centers were divided equally between University of California, San Francisco (UCSF) and center-specific criteria when choosing patients with HCC for LT, and most (65%) did not have separate transplant criteria for deceased donor LT and living donor LT (LDLT). Most centers (56%) preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion. Positron-emission tomography-computed tomography (CT) was the modality of choice for metastatic workup in the majority of centers (74%). Downstaging was the preferred option for over 90% of the centers and included transarterial chemoembolization, transarterial radioembolization, stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications. The alpha-fetoprotein (AFP) cut-off was used by 74% of centers to decide on transplantation as well as to downstage tumors, even if they met the criteria. The criteria for successful downstaging varied, but most centers conformed to the UCSF or their center-specific criteria for LT, along with the AFP cutoff values. The wait time for LT from down staging was at least 4-6 wk in all centers. Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52% of the centers. Approximately 65% of the centers preferred to start everolimus between 1 and 3 months post-LT. CONCLUSION: The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.
ABSTRACT
In Zambia, women with breast symptoms travel through multiple levels of the healthcare system before obtaining a definitive diagnosis. To eradicate this critical barrier to care, we nested a novel breast specialty service platform inside a large public-sector primary healthcare facility in Lusaka, Zambia to offer clinical breast examination, breast ultrasound, and ultrasound-guided core needle biopsy in a one-stop format, tightly linked to referral for treatment. The objective of the study was to determine the life expectancy and survival outcomes of a prospective cohort of women diagnosed with breast cancer who were attended to and followed up at the clinic. The effect of breast cancer stage on prognosis was determined by estimating stage-specific crude survival using the Kaplan-Meier method. Survival analysis was used to estimate mean lifespan according to age and stage at diagnosis. We enrolled 302 women with histologically confirmed breast cancer. The overall 3-year survival was 73%. An increase in patients presenting with early breast cancer and improvements in their survival were observed. Women with early-stage breast cancer had a lifespan similar to the general population, while loss of life expectancy was significant at more advanced stages of disease. Our findings suggest that implementing efficient breast care services at the primary care level can avert a substantial proportion of breast cancer-related deaths. The mitigating factor appears to be stage of disease at the time of diagnosis, the cause of which is multifactorial, with the most influential being delays in the referral process.
Subject(s)
Breast Neoplasms , Primary Health Care , Humans , Female , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Middle Aged , Adult , Prospective Studies , Aged , Zambia/epidemiology , Prognosis , Referral and Consultation , Neoplasm Staging , Life ExpectancyABSTRACT
Imaging-guided photodynamic therapy (PDT) holds great potential for tumor therapy. However, achieving the synergistic enhancement of the reactive oxygen species (ROS) generation efficiency and fluorescence emission of photosensitizers (PSs) remains a challenge, resulting in suboptimal image guidance and theranostic efficacy. The hypoxic tumor microenvironment also hinders the efficacy of PDT. Herein, we propose a "two-stage rocket-propelled" photosensitive system for tumor cell ablation. This system utilizes MitoS, a mitochondria-targeted PS, to ablate tumor cells. Importantly, MitoS can react with HClO to generate a more efficient PS, MitoSO, with a significantly improved fluorescence quantum yield. Both MitoS and MitoSO exhibit less O2-dependent type I ROS generation capability, inducing apoptosis and ferroptosis. In vivo PDT results confirm that this mitochondrial-specific type I-II cascade phototherapeutic strategy is a potent intervention for tumor downstaging. This study not only sheds light on the correlation between the PS structure and the ROS generation pathway but also proposes a novel and effective strategy for tumor downstaging intervention.
Subject(s)
Neoplasms , Photochemotherapy , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/chemistry , Photochemotherapy/methods , Precision Medicine , Reactive Oxygen Species/metabolism , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Mitochondria/metabolism , Cell Line, Tumor , Theranostic Nanomedicine/methods , Tumor MicroenvironmentABSTRACT
Sequential regimens in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) can overcome tyrosine kinase inhibitor (TKI) resistance and maximize clinical benefit. Patients with advanced NSCLC can achieve excellent tumor control after a period of EGFR-TKI treatment. Patients may benefit from additional local treatment, such as surgery or radiation therapy, once the tumor is under control. Here, we present a case of a patient with advanced oligometastatic NSCLC with EGFR mutations who achieved downstaging through sequential EGFR-TKI-based precision medicine allowing resection of residual disease.
Subject(s)
Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Lung Neoplasms , Protein Kinase Inhibitors , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Protein Kinase Inhibitors/therapeutic use , ErbB Receptors/genetics , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/surgery , Male , Middle Aged , Mutation , Neoplasm Metastasis , Female , AgedABSTRACT
Atezolizumab plus bevacizumab is the preferred first-line treatment regimen for patients with advanced hepatocellular carcinoma. Limited data have shown promising results with the use of immune checkpoint inhibitors like nivolumab to downstage these patients for liver transplantation (LT). Here, we describe the first case of successful downstaging with atezolizumab plus bevacizumab in a patient with multifocal hepatocellular carcinoma and main portal vein tumoral thrombosis, followed by ABO-incompatible live donor LT. This illustrated case highlights that atezolizumab plus bevacizumab therapy may be a potential bridging tool for curative LT.
Subject(s)
Antibodies, Monoclonal, Humanized , Bevacizumab , Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Portal Vein , Venous Thrombosis , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/complications , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Liver Neoplasms/complications , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Portal Vein/pathology , Male , Venous Thrombosis/etiology , Venous Thrombosis/drug therapy , Venous Thrombosis/therapy , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , PrognosisABSTRACT
Liver transplantation (LT) is the primary treatment for patients with early-stage hepatocellular carcinoma (HCC). However, the 5-year survival rate after LT remains low for patients with advanced HCC. Recently, combining programmed cell death protein-1 (PD-1) inhibitors with hepatic arterial infusion chemotherapy (HAIC) has achieved promising outcomes in advanced HCC treatment. However, there is a lack of sufficient clinical data demonstrating its effectiveness as a pre-LT down-staging treatment. The current study presented a case of advanced HCC beyond the Milan criteria who underwent LT and achieved a favorable outcome following PD-1 inhibitor combined with FOLFOX-HAIC therapy. Of note, due to treatment-induced tumor necrosis, precise post-treatment tumor size evaluation became challenging. To address this, circulating tumor DNA (ct-DNA) clearance was used as the LT criterion. After three cycles of Pembrolizumab and FOLFOX-HAIC therapy, the patient's serum ctDNA became undetectable and serum α-fetoprotein levels returned to normal. Magnetic resonance imaging results also revealed a significant reduction in liver tumor size post down-staging treatment. Subsequent to LT, serum ctDNA was monitored every two months, consistently yielding diminished results. There were no clinical signs of recurrence 19 months post-LT. These findings suggest that Pembrolizumab in combination with FOLFOX-HAIC may serve as a potential down-staging strategy prior to LT. In addition, ctDNA clearance may be considered a viable biomarker for LT eligibility.
ABSTRACT
About 80% of hepatocellular carcinoma (HCC) patients are in advanced stages and ineligible for curative surgery. Palliative treatments just maintained limited survival, thus an effective downstaging therapy is badly needed. Here we report an initially unresectable patient who underwent radical hepatectomy after successful downstaging with selective internal radiation therapy (SIRT). A 34-year-old man was diagnosed with China Liver Cancer Staging (CNLC) IIIa HCC. Due to insufficient future liver remnant and vascular involvement, the patient was suggested to be unresectable. SIRT with yttrium-90 resin microspheres was given. At three months post-SIRT, a complete response was achieved. The tumor was downstaged to CNLC Ia stage. The patient underwent anatomical hepatectomy 5 months after SIRT. Histopathological examination of the resected specimen showed 4% viable tumor cells inside a necrotic mass. To our knowledge, this is the first case who underwent SIRT with yttrium-90 resin microspheres in China mainland. The success of the downstaging in this case renders a possible cure to be achieved in an initially unresectable patient. In addition, the nearly complete tumor necrosis in the resected specimen indicates a good prognosis post-surgery. This is the first case who underwent SIRT with yttrium-90 resin microspheres in China mainland. SIRT followed by anatomical hepatectomy is a potentially curative strategy for unresectable HCC, which deserves a confirmative trial in the future.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Male , Humans , Adult , Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/radiotherapy , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Hepatectomy , Microspheres , Yttrium Radioisotopes/therapeutic useABSTRACT
Patients with locally advanced hepatocellular cancer (HCC) and portal vein tumor thrombosis (PVTT) have a dismal prognosis since limited treatment options are available for them. In recent years, effective systemic therapy, and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy, have given some hope to prolong survival in them. This review summarized recent evidence in literature regarding the possible role of liver resection (LR) and liver transplantation (LT) in patients with locally advanced HCC and PVTT with no extrahepatic disease. Downstaging therapies have helped make curative resection or LT a reality in selected patients. This review emphasizes on the key points to focus on when considering surgery in these patients, who are usually relegated to palliative systemic therapy alone. Meticulous patient selection based on tumor biology, documented downstaging based on imaging and decrease in tumor marker levels, and an adequate waiting period to demonstrate stable disease, may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Venous Thrombosis , Humans , Liver Neoplasms/complications , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Transplantation/adverse effects , Portal Vein/diagnostic imaging , Portal Vein/surgery , Portal Vein/pathology , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/etiology , Venous Thrombosis/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: The role of neoadjuvant chemotherapy (NAC) in advanced sigmoid colon carcinoma remains to be further characterized. Rationale for NAC includes downstaging on final pathology and optimization of microscopically negative margins (R0 resection). We investigated rates of neoadjuvant chemotherapy use in advanced sigmoid colon cancer at academic cancer centers and assessed factors associated with likelihood of NAC administration. METHODS: The National Cancer Database was queried from 2004 to 2017 for patients with clinical T3 or T4, N0-2, M0 sigmoid colon cancer who underwent surgical resection. Those with neoadjuvant radiation or metastatic disease were excluded. The outcomes of patients who did and did not receive neoadjuvant chemotherapy were evaluated for this retrospective cohort study. RESULTS: There were 23,597 patients of whom 364 (1.5%) received NAC. More patients received NAC at academic (41%, P < .001) and high-volume centers (27%, P < .001). Patients with Medicare/Medicaid (39%) and private insurance (52%) were more likely to receive NAC (P < .001). There was a significantly higher rate of N2 to N1 downstaging in the NAC group. Propensity-score matching demonstrated comprehensive community cancer programs (CCCP) were less likely to provide NAC (OR 0.4; 95% CI 0.23, 0.70, P < .001). There was no difference in survival (P = .20), R0 resection (P = .090), or 30-day readmission rates (P = .30) in the NAC cohort compared to the non-NAC cohort. CONCLUSIONS: Access to centers offering multi-disciplinary care with NAC prior to surgical resection is important. This care was associated with academic and high-volume centers and private or government-sponsored insurance. There was no difference in survival between NAC and non-NAC cohort.