Journal of the National Comprehensive Cancer Network最新文献

Background: The purpose of this study was to evaluate the efficacy and safety of PD-1 blockade combined with cisplatin and paclitaxel (TP)-based chemotherapy as first-line treatment for advanced penile squamous cell carcinoma (PSCC).

Patients and methods: A retrospective review was performed of 32 eligible patients with high-risk stage IV (cN3M0-1) PSCC who received first-line PD-1 blockade combined with TP-based chemotherapy at 5 medical centers (2019-2023). Clinical responses were assessed using RECIST version 1.1. Treatment-related adverse events (TrAEs) and postsurgical complications were graded according to CTCAE version 5.0. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Multiplex immunofluorescence was used to explore potential biomarkers and to present the tumor microenvironment landscape before and after treatment.

Results: After a median treatment duration of 4 cycles (range, 2-6), the overall objective response rate was 78.1% (25/32). Among 27 patients with locally advanced PSCC, 13 (48.1%) subsequently underwent consolidative surgery and 6 (22.2%) achieved a pathologic complete response (pCR). Additionally, 8 (25.0%) patients in the overall cohort underwent consolidated radiotherapy. Median follow-up was 21.1 months (95% CI, 14.1-42.7). Median PFS and OS were 15.0 months (95% CI, 11.4-not available [NA]) and 19.3 months (95% CI, 16.7-NA), respectively. All patients experienced TrAEs, with 50% (16/32) of them having grade ≥3 TrAEs. Higher intratumoral CD8+ T-cell infiltration was observed in pretreatment samples of responders compared with nonresponders (P=.03). CD4+ T-cells, natural killer cells, and macrophages, among others, exhibited significant changes after treatment (all P<.05), suggesting their potential involvement in the antitumor response to immunochemotherapy.

Conclusions: PD-1 blockade plus TP-based chemotherapy was effective and well tolerated, with favorable survival outcomes for patients with stage IV PSCC. High pretreatment intratumoral CD8+ T-cell infiltration may help to identify potential responders.

Prostate cancer survivors represent a growing population of patients with a diagnosis of prostate cancer, whether they were cured using local therapies or continue to receive systemic treatment of advanced disease. Many patients receive androgen deprivation therapy (ADT) during treatment, which is associated with many long-lasting physical and psychological effects. Identifying and addressing the needs of survivors is imperative for improving their health and well-being. This narrative review highlights the most common issues associated with ADT affecting survivorship in prostate cancer, including cardiovascular and metabolic effects, musculoskeletal health, sexual morbidity, and local therapy effects, as well as the mental and psychological toll. A special emphasis is placed on the existing literature examining specific interventions to alleviate these symptoms, along with describing existing gaps in knowledge, with the goal of promoting dedicated studies aimed at enhancing the survivorship experience of patients with prostate cancer.

Background: Neuroendocrine tumors (NETs) of the appendix are typically detected incidentally during appendectomy. Recent studies reported no metachronous metastases among patients with primary tumors <2 cm, regardless of lymph node status or referral for completion hemicolectomy. However, questions persist regarding the possibility of metastases developing decades after surgical resection, particularly because appendiceal NETs are frequently diagnosed in young adults and children. Therefore, we sought to evaluate patients with metastatic appendiceal NETs to assess whether any had been diagnosed previously with an early-stage appendiceal NET.

Methods: We analyzed a large institutional neuroendocrine tumor database to identify appendiceal NETs of all stages and ascertain whether any patients with localized tumors developed metastases and whether any with metastatic disease had initially presented with an early-stage tumor.

Results: Of 3,795 patients with gastroenteropancreatic (GEP) NETs seen in an oncologic NET clinic between January 2008 and August 2023, 124 presented with appendiceal NETs. Of these, only 10 (<0.3% of the total GEP-NET population) had stage IV disease, 8 of whom were diagnosed synchronously at the time of initial diagnosis. Two patients with metastatic disease had reportedly undergone surgical resection for a primary appendiceal NET approximately 20 years before the diagnosis of metastatic disease, but medical records were not available to confirm an appendiceal primary.

Conclusions: Stage IV appendiceal NETs are exceptionally rare, and distant metastases are synchronous in nearly all cases. The risk of metastatic spread after resection of local appendiceal NETs is negligible. Patients with tumors <2 cm should not be managed with completion right hemicolectomy, and the role of this operation for larger tumors is questionable. Postoperative surveillance is unlikely to be of benefit.

Background: Definitive radiotherapy (dRT) has been shown to be an effective option for patients with oligometastatic and oligoprogressive cancers; however, this approach has not been well-studied in metastatic thyroid cancer.

Methods: This retrospective cohort included 119 patients with oligometastatic (34%) and oligoprogressive (66%) metastatic thyroid cancer treated from 2005 to 2024 with 207 dRT courses for 344 sites (50% thoracic, 37% bone, 7.5% brain, 4% abdominopelvic, and 1.5% neck/skull base). Histologies included 61% papillary, 15% poorly differentiated, 13% follicular, and 10% oncocytic, and 114 (96%) patients had radioiodine-refractory disease prior to dRT. Each course involved 1 to 5 sites, with prescriptions intended for definitive control (median BED10, 72 Gy), and palliative RT was excluded. Somatic mutation testing for oncologic drivers was performed in 103 (87%) patients.

Results: Each patient had an average of 3 sites (range, 1-23) treated over 2 courses (range, 1-9). Follow-up from first dRT was a median 2.5 years, with overall survival at 3 and 5 years of 81.5% and 70%, respectively. Actuarial local control per site was 91% at 3 years. Median progression-free survival (PFS) after first course was 17 months (95% CI, 10-24 months), with poorly differentiated histology associated with worse outcomes (hazard ratio [HR], 2.20; 95% CI, 1.24-3.90; P=.007), BRAF mutation with improved PFS (HR, 0.59; 95% CI, 0.37-0.95; P=.029), and no significant findings with respect to systemic therapy. At initial dRT, 92 (77%) patients were not on systemic therapy; and after first dRT, freedom from systemic therapy escalation was a median 4.1 years (95% CI, 1.7-6.5 years), with 2- and 5-year continued deferral rates of 73% and 46%, respectively. Grade 3 toxicities were noted for 1.5% of courses, with no grade 4-5 events observed.

Conclusions: This study underscores the potential of dRT as a feasible strategy for deferring systemic therapy escalation in patients with oligometastatic and oligoprogressive metastatic thyroid cancer, demonstrating that sequential dRT courses impart excellent local control and are safe to deliver repeatedly for multiple distant sites. Further studies are warranted to validate these findings and elucidate the full benefit of dRT as part of a multidisciplinary approach for metastatic thyroid cancer.

Background: Frailty is emerging as an important determinant for quality of life (QoL) and emotional health in older patients with cancer, and specifically in long-term prostate cancer survivors, but quantitative studies are lacking. The current study assesses the prevalence of frailty and its association with QoL and emotional health in long-term prostate cancer survivors after radical prostatectomy.

Patients and methods: A total of 2,979 prostate cancer survivors from the multicenter German Familial Prostate Cancer cohort completed questionnaires on frailty (Groningen Frailty Indicator [GFI]), QoL (EORTC QoL Questionnaire-Core 30), and emotional health (anxiety/depression symptoms via the Patient Health Questionnaire-4). Modified Poisson regression analysis was used to assess factors associated with frailty.

Results: Average patient age was 79.4 years [SD, 6.4 years] and average time since radical prostatectomy was 17.4 years [SD, 3.8 years]. Among the cohort, 33.1% (n=985) of patients were classified as frail (GFI ≥4). Frail patients reported worse emotional health than nonfrail patients (depression symptoms: 24.0% vs 4.0%; anxiety symptoms: 20.6% vs 2.0%; both P<.001) and lower QoL (mean [SD], 53.4 [19.2] vs 72.7 [16.0]); P<.001). Higher age (relative risk [RR], 1.02; 95% CI, 1.01-1.03) and worse depressive (RR, 1.18; 95% CI, 1.12-1.24) and anxiety symptoms (RR, 1.17; 95% CI, 1.11-1.23) were associated with frailty. Living in a partnership (RR, 0.76; 95% CI, 0.67-0.86) and a higher QoL (RR, 0.86 for a 10-point increase; 95% CI, 0.84-0.89) were associated with nonfrailty.

Conclusions: In a large German cohort, every third long-term prostate cancer survivor after radical prostatectomy was frail. The association of frailty with lower QoL and poorer mental health indicates the need for an integrated care approach including further geriatric assessment and possible interventions to improve health outcomes targeted to frail patients.

Background: Widespread adoption of secure messaging (SM) provides patients with cancer with unprecedented access to medical providers at the expense of increased workload for oncologists. Herein, we analyze oncology SM clinical content and acuity and translate these to estimated cost savings from reduced appointments.

Methods: This population-based retrospective cohort study examined the content of patient-initiated SM threads exchanged through the patient portal website or app over 1 year (June 1, 2021-May 31, 2022) at 21 Kaiser Permanente Northern California oncology practices, which typically do not have patient copayments associated with SM. A random sample of 500 SM threads were reviewed and categorized by message content, acuity, and appropriate level of service. Cost and time estimates were used to compare the cost of SM management by oncologists alone versus assisted by medical assistants and nurses.

Results: During the study, 41,272 patients initiated 334,053 unique SM threads to 132 oncologists. Of the SM threads reviewed, only 26.8% required oncologist expertise. Based on thread content, the remaining 73.2% may have been better managed by a nurse (38.2%), medical assistant (28.4%), primary care physician (5.4%), or another subspecialty provider (1.2%). Emergency care was recommended in 2.4% of the threads reviewed. Significant medical care was provided to patients in 24.4% of the reviewed threads that would typically require an appointment. We estimate that the SM exchanges provided $11.2 million in care, including $3.6 million in avoided out-of-pocket copayment costs to patients and $7.6 million in missed billing codes.

Conclusions: High utilization of SM generates additional workload for oncologists that could mostly be appropriately managed by alternate providers. The magnitude of unreimbursed medical care provided via SM and the use of SM for emergent medical situations creates an urgent need for new practice models. An alternative architecture for triaging, managing, and billing SM could reduce costs and oncologist burnout.

In patients with surgically resectable colon cancer (CC), clinicopathologic characteristics translate into cancer staging and predict recurrence risk. Adjuvant chemotherapy reduces the risk of recurrence and is offered to high-risk patients. However, some patients are inevitably overtreated or undertreated; better risk stratification is necessary to improve outcomes after surgery. Circulating tumor DNA (ctDNA)-based minimum residual disease (MRD) assays sequence plasma cell-free DNA for tumor DNA to predict the presence of otherwise subclinical malignancy. Studies have demonstrated that detectable ctDNA after surgery for CC predicts a high rate of recurrence and improves prognostication. Recent clinical trials show promise for using ctDNA to guide therapy, in particular standard-risk stage II CC. Large, randomized studies evaluating ctDNA-guided adjuvant chemotherapy versus standard of care in stage III CC are ongoing. Current data are insufficient to recommend routine use of ctDNA to guide adjuvant chemotherapy in resectable stage III CC.

Background: There is growing evidence that bridge to surgery with stent or decompressing stoma for left-sided obstructive colon cancer (LSOCC) is better than emergency resection (ER), especially in elderly patients (age ≥70 years). This was already incorporated in Dutch guideline recommendations in 2014. The aim of this study was to evaluate time trends and interhospital variability in treatment approaches for LSOCC, and to compare short-term outcomes between approaches.

Patients and methods: Data of patients undergoing resection for LSOCC between 2012 and 2020 were extracted from the Dutch ColoRectal Audit.

Results: A total of 4,535 patients were included (3,155 ER, 573 semielective resection [SER], 807 resection after stent or stoma [RSS]). A decrease in ER over time was observed (79.7% in 2012-2014, 68.8% in 2015-2017, and 54.7% in 2018-2020) in favor of RSS (9.2%, 17.9%, and 31.2%, respectively). Compared with SER and RSS, ER was associated with higher 30-day mortality (6.2% ER, 2.8% SER, and 1.0% RSS; P<.001) and complication rates (45.4%, 31.2%, 31.5%, respectively; P<.001). There were still 19 hospitals with >75% ER in 2018-2020. For hospitals with >75% ER, mortality was significantly higher compared with hospitals mainly performing SER and RSS (5.6% vs 4.2%; P=.038). The proportion of ER in patients (age ≥70 years) decreased from 80.7% in 2012-2014 to 54.3% in 2018-2020 (P<.001). Mortality in patients aged ≥70 years was significantly lower after RSS than after ER (1.6% vs 9.5%; P<.001).

Conclusions: A significant decrease in ER for LSOCC at a national level was observed, although with a variable degree of adherence to revised guidelines among hospitals. The high risk of mortality after ER, especially in elderly patients, strongly supports the guideline recommendations to perform bridge to surgery in these patients.