Antonio Ghidini - Academia.edu (original) (raw)
Papers by Antonio Ghidini
NEJM, 2024
To the Editor: Results of the phase 3 ADRIATIC trial (Oct. 10 issue) 1 marked a breakthrough in t... more To the Editor: Results of the phase 3 ADRIATIC trial (Oct. 10 issue) 1 marked a breakthrough in the treatment of limited-stage small-cell lung cancer, but some questions remain unanswered. According to the protocol, the radiotherapy dose was 60 to 66 Gy once daily or 45 Gy twice daily. Are these doses the best options for limited-stage small-cell lung cancer? In a randomized phase 2 trial, Gronberg et al. 2 found that high-dose thoracic radiotherapy of 60 Gy twice daily improved survival as compared with the standard dose of 45 Gy twice daily (hazard ratio for death from any cause, 0.61; 95% confidence interval, 0.41 to 0.90). The authors also observed that the high-dose regimen led to the longest median overall survival duration (43.5 months) 3 that has been reported in trials of chemoradiotherapy for limited-stage small-cell lung cancer. [4][5][6] Although this trial is a phase 2 trial with a limited sample size, it has remarkable clinical relevance, with an absolute effect of 18 fewer deaths per 100 patients treated (number needed to treat to avoid one death, 5; range, 3 to 25). Notwithstanding the impressive results of the ADRIATIC trial, will we be compelled to use a less effective radiation schedule such as that in the trial? The scientific world is called to answer this question, and efforts should be made to add evidence in this area.
Cancers (Basel), 2024
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Cancer epidemiology, Aug 1, 2024
Current problems in cancer, Jun 1, 2024
There are multiple neoadjuvant regimens, including platinum agents for triplenegative breast canc... more There are multiple neoadjuvant regimens, including platinum agents for triplenegative breast cancer (TNBC), each with a different safety profile, outcome, and pathologic complete response rate (pCR%). We performed a systematic review and network meta-analysis to compare the efficacy and safety of different platinum-based neoadjuvant CT treatments for TNBC. Methods: Bibliographic databases (PubMed, Embase, and Cochrane Library) were searched from their inception to October 31, 2022. Eligible studies were randomized clinical trials that evaluated the addition of carboplatin or cisplatin to standard neoadjuvant CT for TNBC. The primary endpoints were pCR rates and DFS/EFS, while the secondary endpoints were grade (G)3-4 hematological toxicity and OS. Results: Thirteen trials involving 3154 patients comparing six treatments (carboplatin AUC 5, carboplatin AUC 6, carboplatin AUC 2, carboplatin AUC 1.5, cisplatin 75 mg/m2, and standard anthracycline-and/or taxane-based CT) were identified. Based on the most effective treatments added to neoadjuvant CT, carboplatin AUC 2 was associated with the least improvement in pCR% (RR, 1.49; 95%CI, 1.23, 1.8), carboplatin AUC 6 was associated with similar improvement in pCR % (RR 1.58, 95%CI, 1.35, 1.84) and carboplatin AUC 5 with the highest improvement in pCR% (RR 2.23, 95%CI, 1.6,32). The treatment associated with the most considerable improvement in DFS when added to neoadjuvant CT was carboplatin AUC 5 (HR 0.36, 95%CI 0.18, 0.73). It was also better than AUC 6 and AUC 2 (HR= 0.45, 95%CI 0.21-0.96 and HR=0.48, 95%CI 0.23-0.98). All schedules exhibited similar outcomes in terms of OS; however, only AUC 2 demonstrated a significant improvement compared to the no-platinum arms. Neutropenia, thrombocytopenia, and anemia G3-4 were significantly increased by carboplatin AUC 6. Conclusions: Based on this network meta-analysis, carboplatin AUC 5 added to standard neoadjuvant CT may provide substantial pCR and DFS benefits with a low toxicity risk compared to other carboplatin doses.
Anti-cancer drugs, Mar 19, 2024
Journal of geriatric oncology/Journal of geriatric oncology (Online), Mar 1, 2024
The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatme... more The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the immune system's capacity to detect and destroy cancer cells. ICIs used in cancer immunotherapy are primarily categorized into two groups: anti-PD-1/L1 and anti-CTLA-4. The application of combination ICI therapy (ICI doublets) in older patients prompts questions about their relative efficacy compared to standard therapies, particularly in comparison to younger patient cohorts. Materials and Methods: This study involved an extensive review of literature from databases including PubMed, Embase, and the Cochrane Register of Controlled Trials. Our primary aim was to assess overall survival (OS) outcomes in a cohort of older patients, specifically those aged 65 and above, undergoing treatment for advanced cancers. The treatment modalities considered included ICI doublets, ICI monotherapy (alone or in combination with non-ICI drugs), and non-ICI therapies. The study aimed to compare the OS outcomes across these different therapeutic approaches. Results: The analysis incorporated data from 18 trials, indicating that patients treated with ICI doublets exhibited a statistically significant improvement in OS compared to the control group (hazard ratio [HR] = 0.9, 95% confidence interval [CI] 0.84-0.96; P < 0.01). The addition of CTLA-4 inhibitors did not show significant advantages over anti-PD-1/L1 monotherapy (HR = 0.92, 95% CI 0.83-1.02; P = 0.13). When compared to non-ICI therapies, such as chemotherapy alone, ICI doublets demonstrated improved OS outcomes (HR = 0.89, 95% CI 0.82-0.97; P < 0.01). Discussion: Our findings suggest that ICI doublets may offer a modest improvement in the outcomes of older cancer patients compared to non-ICI-based treatments. Consequently, the use of ICI doublets in older patients should be considered on an individual basis, prioritizing cases where there are clear advantages over conventional therapy. This study underscores the importance of developing personalized treatment strategies for older patients, necessitating a cautious and individualized approach in medication selection.
Clin Nutr ESPEN, 2024
Introduction: Vitamin D3, which originates from cholesterol, exerts its influence on immune cells... more Introduction: Vitamin D3, which originates from cholesterol, exerts its influence on immune cells and potentially cancer cells via the metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D3), impacting their proliferation, differentiation, and apoptosis. An umbrella review was conducted to evaluate the potential protective effect of vitamin D3 intake and serum levels on the incidence and mortality of cancer. Material and methods: A systematic search was conducted in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE databases from their inception to October 1, 2023. We included meta-analyses of observational or randomized clinical trials that compared interventions (vitamin D3 intake) or blood levels in a healthy population, with cancer incidence or mortality as outcomes. The grading of evidence certainty followed established criteria, including strong, highly suggestive, suggestive, weak, or not significant. Results: A total of 71 systematic reviews were included. Strong evidence indicated that vitamin D3 supplementation reduced total cancer mortality (odds ratio [OR], 0.9 [95% CI, 0.87-0.92]; P<.01). In the context of site-specific cancers, there exists highly suggestive evidence pointing towards the potential prevention of head and neck, breast, colorectal, lung, and renal cell cancers through the intake of vitamin D3. Furthermore, strong evidence suggests that maintaining sufficient levels of vitamin D3 may effectively lower the risk of renal cell and thyroid cancer (OR=0.76 [95%CI 0.64-0.88]). Conclusions: There is significant evidence that vitamin D3 intake may reduce the incidence of some cancers. Routine assessments to ensure sufficient levels of vitamin D3 and administering supplements to address deficiencies may serve as crucial preventive measures for healthcare systems.
There are multiple neoadjuvant regimens, including platinum agents for triplenegative breast canc... more There are multiple neoadjuvant regimens, including platinum agents for triplenegative breast cancer (TNBC), each with a different safety profile, outcome, and pathologic complete response rate (pCR%). We performed a systematic review and network meta-analysis to compare the efficacy and safety of different platinum-based neoadjuvant CT treatments for TNBC. Methods: Bibliographic databases (PubMed, Embase, and Cochrane Library) were searched from their inception to October 31, 2022. Eligible studies were randomized clinical trials that evaluated the addition of carboplatin or cisplatin to standard neoadjuvant CT for TNBC. The primary endpoints were pCR rates and DFS/EFS, while the secondary endpoints were grade (G)3-4 hematological toxicity and OS. Results: Thirteen trials involving 3154 patients comparing six treatments (carboplatin AUC 5, carboplatin AUC 6, carboplatin AUC 2, carboplatin AUC 1.5, cisplatin 75 mg/m2, and standard anthracycline-and/or taxane-based CT) were identified. Based on the most effective treatments added to neoadjuvant CT, carboplatin AUC 2 was associated with the least improvement in pCR% (RR, 1.49; 95%CI, 1.23, 1.8), carboplatin AUC 6 was associated with similar improvement in pCR % (RR 1.58, 95%CI, 1.35, 1.84) and carboplatin AUC 5 with the highest improvement in pCR% (RR 2.23, 95%CI, 1.6,32). The treatment associated with the most considerable improvement in DFS when added to neoadjuvant CT was carboplatin AUC 5 (HR 0.36, 95%CI 0.18, 0.73). It was also better than AUC 6 and AUC 2 (HR= 0.45, 95%CI 0.21-0.96 and HR=0.48, 95%CI 0.23-0.98). All schedules exhibited similar outcomes in terms of OS; however, only AUC 2 demonstrated a significant improvement compared to the no-platinum arms. Neutropenia, thrombocytopenia, and anemia G3-4 were significantly increased by carboplatin AUC 6. Conclusions: Based on this network meta-analysis, carboplatin AUC 5 added to standard neoadjuvant CT may provide substantial pCR and DFS benefits with a low toxicity risk compared to other carboplatin doses.
Journal of Geriatric Oncology, 2024
The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatme... more The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the immune system's capacity to detect and destroy cancer cells. ICIs used in cancer immunotherapy are primarily categorized into two groups: anti-PD-1/L1 and anti-CTLA-4. The application of combination ICI therapy (ICI doublets) in older patients prompts questions about their relative efficacy compared to standard therapies, particularly in comparison to younger patient cohorts. Materials and Methods: This study involved an extensive review of literature from databases including PubMed, Embase, and the Cochrane Register of Controlled Trials. Our primary aim was to assess overall survival (OS) outcomes in a cohort of older patients, specifically those aged 65 and above, undergoing treatment for advanced cancers. The treatment modalities considered included ICI doublets, ICI monotherapy (alone or in combination with non-ICI drugs), and non-ICI therapies. The study aimed to compare the OS outcomes across these different therapeutic approaches. Results: The analysis incorporated data from 18 trials, indicating that patients treated with ICI doublets exhibited a statistically significant improvement in OS compared to the control group (hazard ratio [HR] = 0.9, 95% confidence interval [CI] 0.84-0.96; P < 0.01). The addition of CTLA-4 inhibitors did not show significant advantages over anti-PD-1/L1 monotherapy (HR = 0.92, 95% CI 0.83-1.02; P = 0.13). When compared to non-ICI therapies, such as chemotherapy alone, ICI doublets demonstrated improved OS outcomes (HR = 0.89, 95% CI 0.82-0.97; P < 0.01). Discussion: Our findings suggest that ICI doublets may offer a modest improvement in the outcomes of older cancer patients compared to non-ICI-based treatments. Consequently, the use of ICI doublets in older patients should be considered on an individual basis, prioritizing cases where there are clear advantages over conventional therapy. This study underscores the importance of developing personalized treatment strategies for older patients, necessitating a cautious and individualized approach in medication selection.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Head & neck, Mar 3, 2022
Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compa... more Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compared with HPV‐counterparts, thereby pushing the adoption of de‐intensification treatment approaches as new strategies to preserve superior oncologic outcomes while minimizing toxicity. We evaluated the effect of treatment de‐intensification in terms of overall survival (OS), progression‐free survival (PFS), locoregional and distant control (LRC and DM) by selecting prospective or retrospective studies, providing outcome data with reduced intensification versus standard curative treatment in HPV+ OPC patients, with a systematic analysis till September 2020. The primary outcome of interest was OS. Secondary endpoints were PFS, LRC, and DM expressed as HR. A total of 55 studies (from 1393 screened references) were employed for quantitative synthesis for 38 929 patients. Among n = 48 studies with data available, de‐intensified treatments reduced OS in HPV+ OPCs (HR = 1.33, 95% CI 1.17–1.52; p < 0.01). In de‐escalated treatments, PFS was also decreased (HR = 2.11, 95% CI 1.65–2.69; p < 0.01). Compared with standard treatments, reduced intensity approaches were associated with reduced locoregional and distant disease control (HR = 2.51, 95% CI 1.75–3.59; p < 0.01; and HR = 1.9, 95% CI 1.25–2.9; p < 0.01). Chemoradiation improved survival in a definitive curative setting compared with radiotherapy alone (HR = 1.42, 95% CI 1.16–1.75; p < 0.01). When adjuvant treatments were compared, standard and de‐escalation strategies provided similar OS. In conclusion, in patients with HPV+ OPC, de‐escalation treatments should not be widely and agnostically adopted in clinical practice, as therein lies a concrete risk of offering a sub‐optimal treatment to patients.
Digestive and Liver Disease, Jun 1, 2023
International Journal of Radiation Oncology Biology Physics, Feb 1, 2017
The purpose of this study is to investigate whether proton radiation therapy and IMRT may improve... more The purpose of this study is to investigate whether proton radiation therapy and IMRT may improve the therapeutic ratio for patients receiving adjuvant radiation therapy following surgery for pancreatic head cancer based on RTOG 0848. Materials/Methods: Ten patients with pancreatic head adenocarcinoma treated with radiation therapy between 2010 and 2013 were included in this study. All patients were simulated with contrast-enhanced CT imaging. All planning volumes were created per RTOG 0848 protocol. A dose of 50.4Gy given in 28 fractions was delivered to the PTV with 95% isodose coverage of at least 95% of the PTV. The organs at risk (OAR) evaluated in this study are the kidneys, liver, small bowel, and spinal cord. Results: The 3D proton plans consistently delivered lower mean total kidney doses, mean liver doses, and liver D 1/3 compared to the IMRT plans. The 3D proton plans also gave less mean liver dose, liver D 1/3 , bowel V 15 , and bowel V 50 in comparison to the 3D photon plans. There was no difference between the IMRT and 3D photon plans in dose delivered to the kidneys, liver, or bowel. See Table for a summary of the results. Conclusions: For patients receiving radiation therapy per ongoing RTOG 0848 for pancreatic cancer, proton plans demonstrate superior organ at risk sparing compared to IMRT photon treatment plans. Protons may provide a means of improving the therapeutic ratio for patients receiving adjuvant radiation therapy.
Neoplasia, Aug 1, 2022
Author contributions: Wong CR drafted the manuscript, contributed to the conception and design, a... more Author contributions: Wong CR drafted the manuscript, contributed to the conception and design, and made revisions for resubmission; Nguyen MH and Lim JK contributed to the conception and design and provided critical revisions of the manuscript.
Cancer Treatment Reviews, Jul 1, 2023
NEJM, 2024
To the Editor: Results of the phase 3 ADRIATIC trial (Oct. 10 issue) 1 marked a breakthrough in t... more To the Editor: Results of the phase 3 ADRIATIC trial (Oct. 10 issue) 1 marked a breakthrough in the treatment of limited-stage small-cell lung cancer, but some questions remain unanswered. According to the protocol, the radiotherapy dose was 60 to 66 Gy once daily or 45 Gy twice daily. Are these doses the best options for limited-stage small-cell lung cancer? In a randomized phase 2 trial, Gronberg et al. 2 found that high-dose thoracic radiotherapy of 60 Gy twice daily improved survival as compared with the standard dose of 45 Gy twice daily (hazard ratio for death from any cause, 0.61; 95% confidence interval, 0.41 to 0.90). The authors also observed that the high-dose regimen led to the longest median overall survival duration (43.5 months) 3 that has been reported in trials of chemoradiotherapy for limited-stage small-cell lung cancer. [4][5][6] Although this trial is a phase 2 trial with a limited sample size, it has remarkable clinical relevance, with an absolute effect of 18 fewer deaths per 100 patients treated (number needed to treat to avoid one death, 5; range, 3 to 25). Notwithstanding the impressive results of the ADRIATIC trial, will we be compelled to use a less effective radiation schedule such as that in the trial? The scientific world is called to answer this question, and efforts should be made to add evidence in this area.
Cancers (Basel), 2024
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Cancer epidemiology, Aug 1, 2024
Current problems in cancer, Jun 1, 2024
There are multiple neoadjuvant regimens, including platinum agents for triplenegative breast canc... more There are multiple neoadjuvant regimens, including platinum agents for triplenegative breast cancer (TNBC), each with a different safety profile, outcome, and pathologic complete response rate (pCR%). We performed a systematic review and network meta-analysis to compare the efficacy and safety of different platinum-based neoadjuvant CT treatments for TNBC. Methods: Bibliographic databases (PubMed, Embase, and Cochrane Library) were searched from their inception to October 31, 2022. Eligible studies were randomized clinical trials that evaluated the addition of carboplatin or cisplatin to standard neoadjuvant CT for TNBC. The primary endpoints were pCR rates and DFS/EFS, while the secondary endpoints were grade (G)3-4 hematological toxicity and OS. Results: Thirteen trials involving 3154 patients comparing six treatments (carboplatin AUC 5, carboplatin AUC 6, carboplatin AUC 2, carboplatin AUC 1.5, cisplatin 75 mg/m2, and standard anthracycline-and/or taxane-based CT) were identified. Based on the most effective treatments added to neoadjuvant CT, carboplatin AUC 2 was associated with the least improvement in pCR% (RR, 1.49; 95%CI, 1.23, 1.8), carboplatin AUC 6 was associated with similar improvement in pCR % (RR 1.58, 95%CI, 1.35, 1.84) and carboplatin AUC 5 with the highest improvement in pCR% (RR 2.23, 95%CI, 1.6,32). The treatment associated with the most considerable improvement in DFS when added to neoadjuvant CT was carboplatin AUC 5 (HR 0.36, 95%CI 0.18, 0.73). It was also better than AUC 6 and AUC 2 (HR= 0.45, 95%CI 0.21-0.96 and HR=0.48, 95%CI 0.23-0.98). All schedules exhibited similar outcomes in terms of OS; however, only AUC 2 demonstrated a significant improvement compared to the no-platinum arms. Neutropenia, thrombocytopenia, and anemia G3-4 were significantly increased by carboplatin AUC 6. Conclusions: Based on this network meta-analysis, carboplatin AUC 5 added to standard neoadjuvant CT may provide substantial pCR and DFS benefits with a low toxicity risk compared to other carboplatin doses.
Anti-cancer drugs, Mar 19, 2024
Journal of geriatric oncology/Journal of geriatric oncology (Online), Mar 1, 2024
The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatme... more The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the immune system's capacity to detect and destroy cancer cells. ICIs used in cancer immunotherapy are primarily categorized into two groups: anti-PD-1/L1 and anti-CTLA-4. The application of combination ICI therapy (ICI doublets) in older patients prompts questions about their relative efficacy compared to standard therapies, particularly in comparison to younger patient cohorts. Materials and Methods: This study involved an extensive review of literature from databases including PubMed, Embase, and the Cochrane Register of Controlled Trials. Our primary aim was to assess overall survival (OS) outcomes in a cohort of older patients, specifically those aged 65 and above, undergoing treatment for advanced cancers. The treatment modalities considered included ICI doublets, ICI monotherapy (alone or in combination with non-ICI drugs), and non-ICI therapies. The study aimed to compare the OS outcomes across these different therapeutic approaches. Results: The analysis incorporated data from 18 trials, indicating that patients treated with ICI doublets exhibited a statistically significant improvement in OS compared to the control group (hazard ratio [HR] = 0.9, 95% confidence interval [CI] 0.84-0.96; P < 0.01). The addition of CTLA-4 inhibitors did not show significant advantages over anti-PD-1/L1 monotherapy (HR = 0.92, 95% CI 0.83-1.02; P = 0.13). When compared to non-ICI therapies, such as chemotherapy alone, ICI doublets demonstrated improved OS outcomes (HR = 0.89, 95% CI 0.82-0.97; P < 0.01). Discussion: Our findings suggest that ICI doublets may offer a modest improvement in the outcomes of older cancer patients compared to non-ICI-based treatments. Consequently, the use of ICI doublets in older patients should be considered on an individual basis, prioritizing cases where there are clear advantages over conventional therapy. This study underscores the importance of developing personalized treatment strategies for older patients, necessitating a cautious and individualized approach in medication selection.
Clin Nutr ESPEN, 2024
Introduction: Vitamin D3, which originates from cholesterol, exerts its influence on immune cells... more Introduction: Vitamin D3, which originates from cholesterol, exerts its influence on immune cells and potentially cancer cells via the metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D3), impacting their proliferation, differentiation, and apoptosis. An umbrella review was conducted to evaluate the potential protective effect of vitamin D3 intake and serum levels on the incidence and mortality of cancer. Material and methods: A systematic search was conducted in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE databases from their inception to October 1, 2023. We included meta-analyses of observational or randomized clinical trials that compared interventions (vitamin D3 intake) or blood levels in a healthy population, with cancer incidence or mortality as outcomes. The grading of evidence certainty followed established criteria, including strong, highly suggestive, suggestive, weak, or not significant. Results: A total of 71 systematic reviews were included. Strong evidence indicated that vitamin D3 supplementation reduced total cancer mortality (odds ratio [OR], 0.9 [95% CI, 0.87-0.92]; P<.01). In the context of site-specific cancers, there exists highly suggestive evidence pointing towards the potential prevention of head and neck, breast, colorectal, lung, and renal cell cancers through the intake of vitamin D3. Furthermore, strong evidence suggests that maintaining sufficient levels of vitamin D3 may effectively lower the risk of renal cell and thyroid cancer (OR=0.76 [95%CI 0.64-0.88]). Conclusions: There is significant evidence that vitamin D3 intake may reduce the incidence of some cancers. Routine assessments to ensure sufficient levels of vitamin D3 and administering supplements to address deficiencies may serve as crucial preventive measures for healthcare systems.
There are multiple neoadjuvant regimens, including platinum agents for triplenegative breast canc... more There are multiple neoadjuvant regimens, including platinum agents for triplenegative breast cancer (TNBC), each with a different safety profile, outcome, and pathologic complete response rate (pCR%). We performed a systematic review and network meta-analysis to compare the efficacy and safety of different platinum-based neoadjuvant CT treatments for TNBC. Methods: Bibliographic databases (PubMed, Embase, and Cochrane Library) were searched from their inception to October 31, 2022. Eligible studies were randomized clinical trials that evaluated the addition of carboplatin or cisplatin to standard neoadjuvant CT for TNBC. The primary endpoints were pCR rates and DFS/EFS, while the secondary endpoints were grade (G)3-4 hematological toxicity and OS. Results: Thirteen trials involving 3154 patients comparing six treatments (carboplatin AUC 5, carboplatin AUC 6, carboplatin AUC 2, carboplatin AUC 1.5, cisplatin 75 mg/m2, and standard anthracycline-and/or taxane-based CT) were identified. Based on the most effective treatments added to neoadjuvant CT, carboplatin AUC 2 was associated with the least improvement in pCR% (RR, 1.49; 95%CI, 1.23, 1.8), carboplatin AUC 6 was associated with similar improvement in pCR % (RR 1.58, 95%CI, 1.35, 1.84) and carboplatin AUC 5 with the highest improvement in pCR% (RR 2.23, 95%CI, 1.6,32). The treatment associated with the most considerable improvement in DFS when added to neoadjuvant CT was carboplatin AUC 5 (HR 0.36, 95%CI 0.18, 0.73). It was also better than AUC 6 and AUC 2 (HR= 0.45, 95%CI 0.21-0.96 and HR=0.48, 95%CI 0.23-0.98). All schedules exhibited similar outcomes in terms of OS; however, only AUC 2 demonstrated a significant improvement compared to the no-platinum arms. Neutropenia, thrombocytopenia, and anemia G3-4 were significantly increased by carboplatin AUC 6. Conclusions: Based on this network meta-analysis, carboplatin AUC 5 added to standard neoadjuvant CT may provide substantial pCR and DFS benefits with a low toxicity risk compared to other carboplatin doses.
Journal of Geriatric Oncology, 2024
The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatme... more The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the immune system's capacity to detect and destroy cancer cells. ICIs used in cancer immunotherapy are primarily categorized into two groups: anti-PD-1/L1 and anti-CTLA-4. The application of combination ICI therapy (ICI doublets) in older patients prompts questions about their relative efficacy compared to standard therapies, particularly in comparison to younger patient cohorts. Materials and Methods: This study involved an extensive review of literature from databases including PubMed, Embase, and the Cochrane Register of Controlled Trials. Our primary aim was to assess overall survival (OS) outcomes in a cohort of older patients, specifically those aged 65 and above, undergoing treatment for advanced cancers. The treatment modalities considered included ICI doublets, ICI monotherapy (alone or in combination with non-ICI drugs), and non-ICI therapies. The study aimed to compare the OS outcomes across these different therapeutic approaches. Results: The analysis incorporated data from 18 trials, indicating that patients treated with ICI doublets exhibited a statistically significant improvement in OS compared to the control group (hazard ratio [HR] = 0.9, 95% confidence interval [CI] 0.84-0.96; P < 0.01). The addition of CTLA-4 inhibitors did not show significant advantages over anti-PD-1/L1 monotherapy (HR = 0.92, 95% CI 0.83-1.02; P = 0.13). When compared to non-ICI therapies, such as chemotherapy alone, ICI doublets demonstrated improved OS outcomes (HR = 0.89, 95% CI 0.82-0.97; P < 0.01). Discussion: Our findings suggest that ICI doublets may offer a modest improvement in the outcomes of older cancer patients compared to non-ICI-based treatments. Consequently, the use of ICI doublets in older patients should be considered on an individual basis, prioritizing cases where there are clear advantages over conventional therapy. This study underscores the importance of developing personalized treatment strategies for older patients, necessitating a cautious and individualized approach in medication selection.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Head & neck, Mar 3, 2022
Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compa... more Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compared with HPV‐counterparts, thereby pushing the adoption of de‐intensification treatment approaches as new strategies to preserve superior oncologic outcomes while minimizing toxicity. We evaluated the effect of treatment de‐intensification in terms of overall survival (OS), progression‐free survival (PFS), locoregional and distant control (LRC and DM) by selecting prospective or retrospective studies, providing outcome data with reduced intensification versus standard curative treatment in HPV+ OPC patients, with a systematic analysis till September 2020. The primary outcome of interest was OS. Secondary endpoints were PFS, LRC, and DM expressed as HR. A total of 55 studies (from 1393 screened references) were employed for quantitative synthesis for 38 929 patients. Among n = 48 studies with data available, de‐intensified treatments reduced OS in HPV+ OPCs (HR = 1.33, 95% CI 1.17–1.52; p < 0.01). In de‐escalated treatments, PFS was also decreased (HR = 2.11, 95% CI 1.65–2.69; p < 0.01). Compared with standard treatments, reduced intensity approaches were associated with reduced locoregional and distant disease control (HR = 2.51, 95% CI 1.75–3.59; p < 0.01; and HR = 1.9, 95% CI 1.25–2.9; p < 0.01). Chemoradiation improved survival in a definitive curative setting compared with radiotherapy alone (HR = 1.42, 95% CI 1.16–1.75; p < 0.01). When adjuvant treatments were compared, standard and de‐escalation strategies provided similar OS. In conclusion, in patients with HPV+ OPC, de‐escalation treatments should not be widely and agnostically adopted in clinical practice, as therein lies a concrete risk of offering a sub‐optimal treatment to patients.
Digestive and Liver Disease, Jun 1, 2023
International Journal of Radiation Oncology Biology Physics, Feb 1, 2017
The purpose of this study is to investigate whether proton radiation therapy and IMRT may improve... more The purpose of this study is to investigate whether proton radiation therapy and IMRT may improve the therapeutic ratio for patients receiving adjuvant radiation therapy following surgery for pancreatic head cancer based on RTOG 0848. Materials/Methods: Ten patients with pancreatic head adenocarcinoma treated with radiation therapy between 2010 and 2013 were included in this study. All patients were simulated with contrast-enhanced CT imaging. All planning volumes were created per RTOG 0848 protocol. A dose of 50.4Gy given in 28 fractions was delivered to the PTV with 95% isodose coverage of at least 95% of the PTV. The organs at risk (OAR) evaluated in this study are the kidneys, liver, small bowel, and spinal cord. Results: The 3D proton plans consistently delivered lower mean total kidney doses, mean liver doses, and liver D 1/3 compared to the IMRT plans. The 3D proton plans also gave less mean liver dose, liver D 1/3 , bowel V 15 , and bowel V 50 in comparison to the 3D photon plans. There was no difference between the IMRT and 3D photon plans in dose delivered to the kidneys, liver, or bowel. See Table for a summary of the results. Conclusions: For patients receiving radiation therapy per ongoing RTOG 0848 for pancreatic cancer, proton plans demonstrate superior organ at risk sparing compared to IMRT photon treatment plans. Protons may provide a means of improving the therapeutic ratio for patients receiving adjuvant radiation therapy.
Neoplasia, Aug 1, 2022
Author contributions: Wong CR drafted the manuscript, contributed to the conception and design, a... more Author contributions: Wong CR drafted the manuscript, contributed to the conception and design, and made revisions for resubmission; Nguyen MH and Lim JK contributed to the conception and design and provided critical revisions of the manuscript.
Cancer Treatment Reviews, Jul 1, 2023