Head and neck cancer is becoming more common, and survival rates are improving. Human papillomavirus-associated oropharyngeal cancer, in particular, is increasing in incidence and is associated with ...an excellent prognosis. However, toxicity from disease and treatment leads to long-term impairment, disability, and handicap. Currently, more than 60% of survivors have unmet needs. As the numbers of survivors increase, current models of care will be increasingly inadequate to meet their needs. Exploration of new strategies and models of care to better address quality-of-life issues and meet the needs of survivors of head and neck cancer is urgently required.
Concerted research efforts over the last three decades have resulted in improved survival and outcomes for patients diagnosed with nasopharyngeal carcinoma (NPC). The evolution of radiotherapy ...techniques has facilitated improved dose delivery to target volumes while reducing dose to the surrounding normal tissue, improving both disease control and quality of life (QoL). In parallel, clinical trials focusing on determining the optimal systemic therapy to use in conjunction with radiotherapy have been largely successful, resulting in improved locoregional, and distant control. As a consequence, neoadjuvant chemotherapy (NACT) prior to definitive chemoradiotherapy has recently emerged as the preferred standard for patients with locally advanced NPC. Two of the major challenges in interpreting toxicity and QoL data from the published literature have been the reliance on: (1) clinician rather than patient reported outcomes; and (2) reporting statistical rather than clinical meaningful differences in measures. Despite the lower rates of toxicity that have been achieved with highly conformal radiotherapy techniques, survivors remain at moderate risk of persistent and long-lasting treatment effects, and the development of late radiation toxicities such as hearing loss, cranial neuropathies and cognitive impairment many years after successful treatment can herald a significant decline in QoL. Future approaches to reduce long-term toxicity will rely on: (1) identifying individual patients most likely to benefit from NACT; (2) development of response-adapted radiation strategies following NACT; and (3) anticipated further dose reductions to organs at risk with proton and particle therapy. With increasing numbers of survivors, many in the prime of their adult life, research to identify, and strategies to address the unmet needs of NPC survivors are required. This contemporary review will summarize our current knowledge of long-term toxicity, QoL and unmet needs of this survivorship group.
Dysphagia is a major head and neck cancer (HNC) issue. Dysphagia-related patient-reported outcome measures (PROMs) are critical for patient-centred assessment and intervention tailoring. This ...systematic review aimed to derive a comprehensive inventory of HNC dysphagia PROMs and appraise their content validity and internal structure. Six electronic databases were searched to February 2023 for studies detailing PROM content validity or internal structure. Eligible PROMs were those developed or validated for HNC, with ≥20% of items related to swallowing. Two independent raters screened citations and full-text articles. Critical appraisal followed COSMIN guidelines. Overall, 114 studies were included, yielding 39 PROMs (17 dysphagia-specific and 22 generic). Of included studies, 33 addressed PROM content validity and 78 internal structure. Of all PROMs, only the SOAL met COSMIN standards for both sufficient content validity and internal structure. Notably, the development of 18 PROMs predated the publication of COSMIN standards. In conclusion, this review identified 39 PROMs addressing dysphagia in HNC, of which only one met COSMIN quality criteria. Given that half of PROMs were developed prior to COSMIN guidelines, future application of current standards is needed to establish their psychometric quality.
Measuring dysphagia-related patient-reported outcomes (PROs) in Head and Neck Cancer (HNC) patients is challenging due to dysphagia's multidimensional impact, causing inconsistency in outcome ...reporting. To address this issue, this study derived a consensus-based core outcome set (COS) for patient-reported dysphagia in HNC clinical trials where swallowing is a primary or secondary endpoint.
A sample of HNC clinicians, researchers, patients, and caregivers participated in a 2-Round Delphi technique. A Delphi survey, containing a comprehensive list of dysphagia-related PROs, was developed. In Round 1, participants rated item importance on a 5-point scale. Items rated ≥4 by >70% advanced to Round 2, where a consensus meeting addressed items with varied opinions, and the Delphi survey with remaining items was completed. Items rated ≥4 by >70% formed the final COS.
Forty-five participants from nine countries were recruited. After Round 1, 40 items were excluded and 64 advanced to Round 2. After Round 2, a 7-outcome COS was established, comprising the domains of dysphagia symptoms, health status and quality of life.
This study achieved consensus among HNC stakeholders on essential dysphagia PROs for HNC clinical trials. It is advisable to include these 7-core concepts in clinical trials involving people with HNC to facilitate treatment comparisons and data synthesis.
•A D2 LND is preferred for curative intent resection with ≥16 LNs assessed for staging.•Gastric cancer surgery should aim to achieve an RO resection margin.•In the metastatic setting, surgery should ...only be considered for palliation of symptoms.•Patients should be referred to higher volume centres.•Laparoscopic resections should be performed to the same standards as open resections.
Gastric adenocarcinoma accounted for 6.8% of new cancer cases and 8.8% of cancer deaths worldwide in 2012. Although resection is the cornerstone for cure, several aspects of surgical intervention remain controversial or sub-optimally applied at the population level. These include staging, extent of lymph node dissection (LND), optimal requirements of LN assessment, minimum resection margins, surgical technique (laparoscopic vs. open), relationship between surgical volumes and patient outcomes, and resection of stage IV gastric cancer.
A systematic review was conducted to inform surgical care.
The evidence included in this systematic review consists of one guideline, seven systematic reviews and 48 primary studies.
All patients should be discussed at a multidisciplinary team meeting and a staging CT of the chest and abdomen should always be performed. Diagnostic laparoscopy should be performed in patients at risk for stage IV disease. A D2 LND is preferred for curative-intent resection in advanced non-metastatic gastric cancer. At least 16 LNs should be assessed for adequate staging of curative-resected gastric cancer. Gastric cancer surgery should aim to achieve an RO resection margin. In the metastatic setting, surgery should only be considered for palliation of symptoms. Patients should be referred to higher volume centres, and those with adequate support to manage potential complications. Laparoscopic resections should be performed to the same standards as open resections.
To refine stage and prognostic group for human papillomavirus (HPV) -related nonmetastatic (M0) oropharyngeal cancer (OPC).
All patients with nonmetastatic (M0) p16-confirmed OPC treated with ...radiotherapy with or without chemotherapy from 2000 to 2010 were included. Overall survival (OS) was compared among TNM stages for patients with HPV-related and HPV-unrelated OPC separately. For HPV-related OPC, recursive partitioning analysis (RPA) derived new RPA stages objectively. Cox regression was used to calculate adjusted hazard ratios (AHRs) to derive AHR stages. The performance of survival prediction of RPA stage and AHR stage was assessed against the current seventh edition TNM stages. Prognostic groups were derived by RPA, combining RPA stage and nonanatomic factors.
The cohort comprised 573 patients with HPV-related OPC and 237 patients with HPV-unrelated OPC, with a median follow-up of 5.1 years. Lower 5-year OS with higher TNM stage was evident for patients with HPV-unrelated OPC (stage I, II, III, and IV 5-year OS: 70%, 58%, 50%, and 30%, respectively; P = .004) but not for patients with HPV-related OPC (stage I, II, III, and IV 5-year OS: 88%, 78%, 71%, and 74%, respectively; P = .56). RPA divided HPV-related OPC into RPA-I (T1-3N0-2b), RPA-II (T1-3N2c), and RPA-III (T4 or N3; 5-year OS: 82%, 76%, and 54%, respectively; P < .001). AHR also yielded a valid classification, but RPA stage demonstrated better survival prediction. A further RPA (including RPA stage, age, and smoking pack-years PYs) derived the following four valid prognostic groups for survival: group I (T1-3N0-N2c_≤ 20 PY), group II (T1-3N0-N2c_> 20 PY), group III (T4 or N3_age ≤ 70), and group IVA (T4 or N3_age > 70; 5-year OS: 89%, 64%, 57%, and 40%, respectively; P < .001).
An RPA-based TNM stage grouping (stage I/II/III: T1-3N0-N2b/T1-3N2c/T4 or N3, with M1 as stage IV) is proposed for HPV-related OPC as a result of significantly improved survival prediction compared with the seventh edition TNM, and prognostication is further improved by an RPA-based prognostic grouping within the American Joint Committee on Cancer/Union for International Cancer Control TNM framework for HPV-related OPC.
To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC).
Eligible patients had locally ...advanced Child-Pugh class A HCC, showed Eastern Cooperative Oncology Group performance status 0-1, and were ineligible for standard local-regional therapies. Sorafenib was dose escalated in 2 strata: (1) low effective irradiated liver volume (veff) < 30% and (2) high veff 30%to 60%. Sorafenib (400 mg daily = dose level 1) was administered for 12 weeks, with 6 fractions SBRT delivered weeks 2 and 3, and escalation to full dose (400 mg twice daily) after 12 weeks as tolerated. Standard 3 + 3 cohorts with dose escalation of sorafenib were planned.
Sixteen patients (4 low veff, median dose 51 Gy; 12 high veff, median dose 33 Gy) were treated at 2 sorafenib dose levels. Of those patients 75% were had Barcelona Clinic Liver Cancer stage C, and 63% had main branch portal vein invasion. In the low veff stratum, no dose-limiting toxicities (DLTs) were observed in 4 patients treated with SBRT and sorafenib 400 mg. Inb the high veff stratum: 2 of 3 evaluable patients treated with sorafenib 400 mg experienced DLT (grade 3 large bowel bleed and grade 4 bowel obstruction 51 and 27 days, respectively, after SBRT). One of 6 evaluable patients at dose level -1 (200 mg once daily) experienced a grade 3 tumor rupture at week 5. Median overall survival and in-field local progression have not been reached. Worsening of Child-Pugh liver function class was seen in 6 of 12 patients in the high veff stratum.
Significant toxicity was observed in the high veff stratum, and concurrent SBRT with sorafenib is not recommended outside a clinical trial.
To describe outcomes of prospective trials of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC).
Two trials of SBRT for patients with active HCC unsuitable for standard ...locoregional therapies were conducted from 2004 to 2010. All patients had Child-Turcotte-Pugh class A disease, with at least 700 mL of non-HCC liver. The SBRT dose range was 24 to 54 Gy in six fractions. Primary end points were toxicity and local control at 1 year (LC1y), defined as no progressive disease (PD) of irradiated HCC by RECIST (Response Evaluation Criteria in Solid Tumors).
A total of 102 patients were evaluable (Trial 1, 2004 to 2007: n = 50; Trial 2, 2007 to 2010: n = 52). Underlying liver disease was hepatitis B in 38% of patients, hepatitis C in 38%, alcohol related in 25%, other in 14%, and none in 7%. Fifty-two percent received prior therapies (no prior sorafenib). TNM stage was III in 66%, and 61% had multiple lesions. Median gross tumor volume was 117.0 mL (range, 1.3 to 1,913.4 mL). Tumor vascular thrombosis (TVT) was present in 55%, and extrahepatic disease was present in 12%. LC1y was 87% (95% CI, 78% to 93%). SBRT dose (hazard ratio HR = 0.96; P = .02) and being in Trial 2 (HR = 0.38; P = .03) were associated with LC1y on univariate analysis. Toxicity ≥ grade 3 was seen in 30% of patients. In seven patients (two with TVT PD), death was possibly related to treatment (1.1 to 7.7 months after SBRT). Median overall survival was 17.0 months (95% CI, 10.4 to 21.3 months), for which only TVT (HR = 2.47; P = .01) and being in Trial 2 (HR = 0.49; P = .01) were significant on multivariate analysis.
These results provide strong rationale for studying SBRT for HCC in a randomized trial.
Opinion statement
A larger proportion of patients with head and neck cancers (HNC) are now surviving, constituting up to 3% of all cancer survivors. This is likely due in part to the increase in ...HPV-related oropharyngeal cancers affecting younger individuals and with a better prognosis and to the improved outcomes of other HNCs as well over the last two decades. Most studies have previously been focusing on improving risk stratification, treatment and disease-related outcomes. Over the last decade, there has been an evolving interest in the field of survivorship care. Despite the collaborative efforts from a multidisciplinary team in managing cancer and treatment-related side-effects and in improving survivors’ overall quality of life (QOL), it has been reported that up to 60–65% of patients have at least one unmet need. The purpose of this article is to review current guidelines for HNC survivorship care and identify areas of unmet need. Over the last 5 years, multiple groups have published guidelines describing survivorship care issues and their possible management. Although a very comprehensive and informative first initiative, multiple issues need to be further evaluated. These include how to best support patients and their partners’ fear of cancer recurrence, to provide coordinated care among all physicians, to identify and meet patients’ needs in local multidisciplinary teams and to institute measures to ensure every individual’s access to high-quality patient-centred care. Furthermore, experts may consider engaging in further dialog with primary care physicians (PCP) to improve sharing of survivorship care. More should be learned about PCPs’ comfort levels in providing such care and whether further steps are required to facilitate a seamless. Transition of care and accessibility to specialized care as needed.
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