Poor tolerability to sunitinib with the standard dosing schedule has become an issue. We retrospectively analyzed the treatment efficacy and the profile of adverse events of 2 weeks of sunitinib ...treatment followed by 1-week-off (Schedule 2/1) and compared the results with the standard dosing schedule with 4 weeks of treatment followed by 2-weeks-off (Schedule 4/2).
From January 2010 until December 2012, 48 patients with metastatic renal cell carcinoma who received at least two cycles of sunitinib as first-line therapy were the subjects of this study. After 2011, we switched to Schedule 2/1 for most patients.
Schedule 2/1 included 26 patients and Schedule 4/2 had 22. The incidence of most adverse events was not significantly different between the two groups except for hand-foot syndrome and diarrhoea, which were observed more frequently in Schedule 4/2 and reached statistical significance. A dose interruption due to adverse events in the first three cycles was significantly lower in Schedule 2/1 patients than in those on Schedule 4/2 (27 versus 53% P = 0.04). With respect to treatment efficacy, the objective response rate tended to be higher in Schedule 4/2 than in Schedule 2/1 (50 versus 32%), and median progression-free survival was longer in patients on Schedule 2/1 than those on Schedule 4/2 (18.4 versus 9.1 months). These differences, however, did not reach statistical significance (P = 0.14, P = 0.13).
Alteration in dosing schedule of sunitinib with 2-weeks-on and 1-week-off showed a lower incidence of dose interruption and a similar oncological outcome compared with the standard dosing schedule of 4-weeks-on and 2-weeks-off.
Background
We aimed to evaluate the effect of sarcopenia, a condition of low muscle mass, on the survival among patients who were undergoing radical nephroureterectomy (RNU) for urothelial carcinoma ...of the upper urinary tract (UCUT).
Methods
We retrospectively reviewed consecutive patients with UCUT (cTanyN0M0) who underwent RNU between 2003 and 2013 at our department and its affiliated institutions. Preoperative computed tomography images were used to calculate each patient’s skeletal muscle index, an indicator of whole-body muscle mass. Sarcopenia was defined according to the sex-specific consensus definitions, based on the patient’s skeletal muscle and body mass indexes. We analyzed the relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RNU to identify factors that predicted patient survival.
Results
A total of 137 patients were included, and 90 patients (65.7 %) were diagnosed with sarcopenia. Compared to the non-sarcopenic patients, the sarcopenic patients had a significant inferior 5-year RFS (48.8 vs. 79.6 %,
p
= 0.0002), CSS (57.1 vs. 92.6 %,
p
< 0.0001), and OS (48.2 vs. 90.6 %,
p
< 0.0001). Multivariate analyses revealed that sarcopenia was an independent predictor of shorter RFS, CSS, and OS (all,
p
< 0.0001).
Conclusions
Sarcopenia was an independent predictor of survival among patients with UCUT who were undergoing RNU.
Serum C-reactive protein (CRP) is reportedly associated with metastatic renal cell carcinoma (mRCC) activity. However, in the era of immune checkpoint inhibitors, the predictive value of CRP is ...unclear. In this study, we investigated the predictive impact of pretreatment CRP levels and early changes in CRP levels for the treatment of mRCC with nivolumab plus ipilimumab (NIVO-IPI) therapy.
Forty-eight patients with mRCC treated with NIVO-IPI as a first-line therapy were retrospectively analyzed. First, patients were divided into 2 groups: initial CRP ≥ 1.0 mg/dL and < 1.0 mg/dL. Progression-free survival (PFS) was compared between the 2 groups. Second, based on the CRP change within the first 3 months of NIVO-IPI, patients were placed in the normal group (CRP remains < 1.0 mg/dL), normalized group (CRP decreased < 1.0 mg/dL), and non–normalized group (CRP remained or increased to ≥ 1.0 mg/dL). The predictive association between CRP change and PFS was evaluated.
PFS was significantly lower in the high initial CRP group (n = 24, 50%) compared to the normal CRP group (n = 24, 50%) (median: 4.3 vs. 28.1 months, P = .03). As for the early CRP change, the normal (2.7 vs. 28.1, P = .0002) and normalized (2.7 vs. 11.0, P = .0094) groups showed significantly higher PFS, compared to the non–normalized group. Meanwhile, there was no significant difference between normal, and normalized groups (P = .51). The objective response rate was higher in the normal (57.1% vs. 18.7%, P = .015) and normalized (81.8 vs. 18.7%, P = .0008) groups, compared to the non–normalized group. Multivariate Cox regression analysis showed that normal Hazard ratio (HR) = 0.15, 95% Confidence interval (CI) = 0.02-0.70, P = .026 and normalized (HR 0.21, 95% CI = 0.05-0.73, P = .015) CRP showed significant association with PFS.
In the NIVO-IPI therapy for mRCC, early changes in CRP could predict PFS. This data may be useful for the early detection of ineffective NIVO-IPI therapy and conversion to subsequent therapies.
This retrospective study evaluated the predictive value of CRP level changes during nivolumab+ipilimumab therapy in 48 metastatic renal cell carcinoma patients. Patients whose CRP levels normalized within 3 months and those with normal CRP levels showed equivalent progression-free survival (PFS). Patients with non–normalized CRP levels showed the shortest PFS. Thus, CRP level changes may help detect early progressive disease.
Objective To assess surgical outcomes between the non-renorrhaphy and renorrhaphy techniques in open partial nephrectomy for ≥T1b renal tumors using volumetric studies. Methods We retrospectively ...analyzed the records of 91 patients with normal contralateral kidneys who underwent both open partial nephrectomy for ≥T1b renal tumors and pre- and postoperative enhanced computed tomography between 2010 and 2014. Volumetric studies to assess vascularized parenchymal volume of the operated kidney were performed within 2 months preoperatively and 6 months postoperatively. Using the non-renorrhaphy technique, we coagulated hemorrhagic areas on the surface of the renal parenchyma by monopolar soft coagulation, while a TachoSil tissue-sealing sheet was placed on the resected bed. Results A total of 50 patients underwent renorrhaphy and 41 patients underwent non-renorrhaphy. Patient backgrounds and R.E.N.A.L. nephrometry scores were not significantly different between the two groups. Cold ischemia time was significantly longer in the renorrhaphy than that in the non-renorrhaphy (52 vs 42 minutes, P = .0162). However, significant differences were not observed in the preservation rate of the vascularized parenchymal mass in the operated kidney (renorrhaphy, 71%; non-renorrhaphy, 70%; P = .5054) and global kidney function (renorrhaphy, 88%; non-renorrhaphy, 90%; P = .3653) between the two groups. Renal artery pseudoaneurysm occurred in 2 cases in both groups. Urinary fistula tended to occur more frequently in non-renorrhaphy (2 cases) than in renorrhaphy (5 cases), though this difference was not statistically significant ( P = .237). Conclusion The non-renorrhaphy technique failed to show a benefit in the preservation of vascularized parenchymal mass of the operated kidney and global renal function for ≥T1b renal tumors compared to the renorrhaphy technique.
Abstract
Objectives
To investigate the long-term follow-up outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma, using real-world data.
Methods
A total of 121 ...patients were treated with nivolumab monotherapy as subsequent therapy after the failure of prior tyrosine kinase inhibitor therapy between January 2013 and December 2021 at four affiliated institutions. To evaluate the outcome after 2 years or more, we selected patients in whom nivolumab therapy was started in December 2019 or earlier because data collection was performed until the end of December 2021.
Results
Seventy-four patients were evaluated. During the median follow-up period of 25.8 months, 62 (84%) and 40 (54%) patients had disease progression and died, respectively. Nivolumab was administered as second-line therapy in 43 patients (58%). The median progression-free survival and overall survival were 5.52 and 31.1 months, respectively, and objective response rate was 36%. There was no difference in progression-free survival or overall survival based on the treatment line of nivolumab (P = 0.915, P = 0.559). The magnitude of tumor response and development of immune-related adverse events were significantly associated with progression-free survival (P < 0.0001, P < 0.0001, respectively) and overall survival (P < 0.0001, P = 0.0002, respectively). Treatment-related adverse events developed in 38 patients (51%), including 33 (45%) who had immune-related adverse events. Steroid administration was needed in nine patients (12%).
Conclusions
The present real-world multi-institution study with long-term follow-up data demonstrates that nivolumab monotherapy is effective for previously treated metastatic renal cell carcinoma, prolonging survival, improving tumor response and has a manageable safety profile.
The real-world data with long-term follow-up indicated that nivolumab monotherapy is effective for previously treated metastatic renal cell carcinoma, prolonging survival, improving tumor response, and has a manageable safety profile.
Objectives To determine the primary site and incidence of lymph node metastases in urothelial carcinoma of the upper urinary tract. Methods From January 1989 to October 2005, we treated 181 patients ...with urothelial carcinoma of the upper urinary tract. The findings of the imaging studies when lymph node metastasis was diagnosed and the pathologic examination findings of the nodal specimens were analyzed. If multiple nodal metastases were present, the largest lymph node was considered the primary site. Results Of the 181 patients, 42 (23.2%) had nodal involvement. Lymphatic metastasis was confirmed pathologically in 23 patients and 19 were clinically considered to have nodal metastasis without pathologic diagnosis because these patients died of the disease with deterioration of nodal involvement during follow-up. In tumors of the right renal pelvis, the primary metastatic sites were the right renal hilar, paracaval, and retrocaval nodes. Tumors of the upper two thirds of the right ureter primarily metastasized to the retrocaval and inter-aortocaval nodes. In tumors of the left renal pelvis, the primary sites were the left renal hilar and para-aortic nodes. Tumors of the upper two thirds of the left ureter primarily metastasized to the para-aortic nodes. Tumors of the lower ureter primarily metastasized inferiorly to the aortic bifurcation. Conclusions Lymphadenectomy for urothelial carcinoma of the right renal pelvis and upper two thirds of the ureter should include a relatively wide area, compared with regional lymph nodes conventionally addressed, encompassing the paracaval, retrocaval, and inter-aortocaval nodes.
Purpose
To clarify the efficacy and safety profile of immune checkpoint inhibitors (ICIs) for elderly patients with metastatic renal cell carcinoma (mRCC).
Methods
We retrospectively evaluated 149 ...mRCC patients treated with nivolumab monotherapy as subsequent therapy (
n
= 89) and nivolumab plus ipilimumab as first-line therapy (
n
= 60) at 5 affiliated institutions. The patients were divided according to age: > 70 (elderly) vs. ≤ 70 years (young). Efficacy was analyzed by comparing progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) between elderly and young patients. Safety was assessed by comparing the incidence rates of immune-related adverse events (irAEs).
Results
In the nivolumab monotherapy group, 34/89 patients (38%) were classified as elderly. There was no significant difference in PFS (
p
= 0.607), OS (
p
= 0.383), ORR (
p
= 0.0699), or DCR (
p
= 0.881) between elderly and young patients. In the nivolumab plus ipilimumab group, 20/60 patients (33%) were classified as elderly. There was no significant difference in PFS (
p
= 0.995), OS (
p
= 0.714), ORR (
p
= 0.763), or DCR (
p
= 1.000) between the two groups. The incidence rate of irAEs was not significantly different in the nivolumab (any grade:
p
= 0.121; grade ≥ 3:
p
= 0.542) or in the nivolumab plus ipilimumab (any grade:
p
= 0.666; grade ≥ 3:
p
= 0.576) group; a higher rate of gastrointestinal irAEs was observed in elderly than in young patients (any grade 15% vs. 3%).
Conclusions
The efficacy and safety of nivolumab monotherapy and nivolumab plus ipilimumab were comparable between elderly and young patients. Thus, chronological age alone should not be a contraindication in the use of ICIs for mRCC.
Background
It remains unclear how early treatment interruption of nivolumab plus ipilimumab due to immune-related adverse events affects the outcome of previously untreated metastatic renal cell ...carcinoma (mRCC).
Objective
To investigate the prognostic impact of the early interruption of nivolumab plus ipilimumab, used as first-line therapy for mRCC.
Patients and Methods
We retrospectively evaluated 59 intermediate- or poor-risk mRCC patients who received nivolumab plus ipilimumab as first-line therapy. Based on whether early treatment interruption was implemented within the initial four treatment cycles (i.e., 3 months) or not, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were compared. The prognostic association was further compared with that of 186 patients treated with tyrosine kinase inhibitors (TKIs) as first-line therapy.
Results
Twenty-three of the 59 patients (39%) experienced interruption of nivolumab plus ipilimumab therapy. The patients with interruption had longer PFS (
p
= 0.0055), similar OS (
p
= 0.366), and likely higher ORR (
p
= 0.0660) than those without interruption. Of the patients treated with TKIs, 60 of 186 (32%) experienced interruption, with shorter PFS (
p
= 0.0121), similar OS (
p
= 0.378), and similar ORR (
p
= 0.738) than those without interruption. In the 23 patients with nivolumab plus ipilimumab interruption, high-dose corticosteroids were administered in seven patients (30%). PFS (
p
= 0.638), OS (
p
= 0.968), or ORR (
p
= 0.760) did not differ based on corticosteroid administration.
Conclusions
Early treatment interruption, which exerted a negative effect for TKIs, was a preferable event for nivolumab plus ipilimumab when considering PFS. Furthermore, early administration of high-dose corticosteroids did not diminish the anti-tumor effect of nivolumab plus ipilimumab.
Background
Little information has been published on the use of tyrosine kinase inhibitors for treatment of patients undergoing hemodialysis (HD). We investigated the efficacy and safety of sorafenib ...for metastatic renal cell carcinoma (mRCC) patients undergoing HD.
Methods
Twenty patients undergoing HD were treated with sorafenib as first-line therapy for mRCC at our hospital between April 2008 and August 2014. Patient medical records were retrospectively reviewed to evaluate the response to sorafenib and treatment-related toxicity.
Results
Fifteen and 5 patients were classified in the intermediate and poor risk groups, respectively, of the Memorial Sloan–Kettering Cancer Center risk model. Eighteen patients had 3 or more metastatic lesions, and 7 patients had metastases in 2 or more organs. Of 16 patients who had previously undergone nephrectomy, 8 were pathologically diagnosed with non-clear-cell carcinoma. The median duration of sorafenib therapy was 4.7 months. Sorafenib was discontinued owing to progressing disease for 15 patients and because of serious adverse events (AE) (≥grade 3) for 4 patients, i.e. subarachnoid hemorrhage, cerebral hemorrhage, sepsis, and syncope for 1 patient each. Median time to progression was 6.3 months, and median overall survival was 14.2 months.
Conclusions
In this study, many patients had unfavorable clinical features, for example poor risk classification and metastases in multiple organs. Although sorafenib treatment of HD patients seems feasible, careful monitoring is needed because of the tendency for a high incidence of serious AE, even when a reduced dose is administered.
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