Feasibility and early clinical impact of precision medicine for late-stage cancer patients in a regional public academic hospital.

AIM: Our goal was to describe a precision medicine program in a regional academic hospital, characterize features of included patients and present early data on clinical impact. MATERIALS AND METHODS: We prospectively included 163 eligible patients with late-stage cancer of any diagnosis from June 2020 to May 2022 in the Proseq Cancer trial. Molecular profiling of new or fresh frozen tumor biopsies was done by WES and RNAseq with parallel sequencing of non-tumoral DNA as individual reference. Cases were presented at a National Molecular Tumor Board (NMTB) for discussion of targeted treatment. Subsequently, patients were followed for at least 7 months. RESULTS: 80% (N = 131) of patients had a successful analysis done, disclosing at least one pathogenic or likely pathogenic variant in 96%. A strongly or potentially druggable variant was found in 19% and 73% of patients, respectively. A germline variant was identified in 2.5%. Median time from trial inclusion to NMTB decision was one month. One third (N = 44) of patients who underwent molecularly profiling were matched with a targeted treatment, however, only 16% were either treated (N = 16) or are waiting for treatment (N = 5), deteriorating performance status being the primary cause of failure. A history of cancer among 1st degree relatives, and a diagnosis of lung or prostate cancer correlated with greater chance of targeted treatment being available. The response rate of targeted treatments was 40%, the clinical benefit rate 53%, and the median time on treatment was 3.8 months. 23% of patients presented at NMTB were recommended clinical trial participation, not dependent on biomarkers. CONCLUSIONS: Precision medicine in end-stage cancer patients is feasible in a regional academic hospital but should continue within the frame of clinical protocols as few patients benefit. Close collaboration with comprehensive cancer centers ensures expert evaluations and equality in access to early clinical trials and modern treatment.

Failure pattern and salvage treatment after radical treatment of head and neck cancer.

Purpose The aim of the study was to test the hypothesis that head and neck cancer (HNC) patients benefit from specialized follow-up (FU), as this strategy ensures timely detection of relapses for successful salvage treatment. This was done by evaluation of the pattern of failure, the temporal distribution of recurrences, and the outcome of salvage treatment in a contemporary cohort of HNC patients. Methods The study evaluated a cohort of 2062 consecutive patients treated with curative intent at Aarhus University Hospital from 1 January 2000 to 31 December 2013. The database of DAHANCA contained recordings of recurrent disease in 567 patients with primary tumors of the larynx, pharynx, oral cavity, nasal cavity, paranasal sinuses and salivary glands. A review of medical records was performed in order to update and supplement the database. Results Failures of the 567 patients were primarily in T-site (65%) followed by N-site (36%) and M-site (22%). The vast majority of the first recurrences occurred within the first years after primary treatment; 62%, 82%, and 91% within the first, second and third year, respectively. Totally, 51% were amenable for salvage treatment, and 44% benefited from salvage in terms of a complete response. Permanent tumor control was observed in 128 patients (23%) after one or two salvage attempts. The highest salvage rate was recorded in patients with primary glottic carcinoma (41%) and the lowest among hypopharyngeal cancers (2%). Asymptomatic recurrence was recorded in 12% of all recurrences and this was found to be a positive prognostic factor for disease-specific survival, as they had significantly better outcome after salvage. Conclusion Our data support the usefulness of specialized FU in terms of early detection of recurrent disease. In particular patients with silent recurrences benefited from early detection, as they had a significantly lower risk ratio of death from primary HNC.

A longitudinal study of follow-up activities after curative treatment for head and neck cancer.

PURPOSE: To test the hypothesis that head and neck cancer (HNC) patients are in need of specialized follow-up (FU). This was done by an evaluation of the FU activities in a cohort of patients followed longitudinally for five years with focus on optimal duration and interval of post-therapeutic follow-up. METHODS: The study evaluated a cohort consisting of 197 consecutive patients with HNC treated at Aarhus University Hospital from 1 January to 31 December 2009. The inclusion criteria was that patients should be deemed free of disease two months after completed primary curative intended treatment or after primary curative salvage. It left 141 patients available for analysis. Data were collected through a medical chart review and from the Danish Head and Neck Cancer Group (DAHANCA) database. Parameters recorded were: regular or extraordinary visit, alarm symptoms, late morbidity and the consequences of these. RESULTS: The 141 patients underwent 1408 FU visits. Only 15 of the 141 patients had no tumor problems or morbidity issues raised at any FU visit. Suspicion of recurrent disease was observed at 207 of the 1408 FU visits, involving 97 patients and resulted in a total of 370 diagnostic procedures; 170 (82%) visits with suspicion of recurrence occurred within 3½ years after end of treatment. A recurrence was verified in 30 patients. Additionally four new primary head and neck cancer was diagnosed during follow-up. There were 1150 visits (82%) involving 135 patients in which late treatment-related morbidity was recorded. Actions taken related to morbidity happened in 71 patients, but no new problems appeared after three years. CONCLUSION: The study document the need of specialized FU, as 86% of all HNC survivors have tumor or severe morbidity issues during FU. The data suggest that 3½-year FU after ended therapy may be sufficient for the majority of patients.

The value of routine follow-up after treatment for head and neck cancer. A national survey from DAHANCA.

BACKGROUND: The post-treatment follow-up is well-integrated in the oncologic care tradition, based on the risk of developing recurrent disease or new primary tumors in treated patients. Furthermore, follow-up serves as an opportunity to monitor treatment effects and to provide clinical care of side effects. In this study we measured the activity and effectiveness of routine follow-up in head and neck cancer and assessed the value of follow-up from the perspectives of both physicians and the patients. PATIENTS AND METHODS: During a period of six weeks a prospective national cross section cohort of 619 patients attending regular follow-up were enrolled. All patients had received intended curative treatment for head and neck cancer and all were followed according to DAHANCA guidelines. Data were collected by the physician filling in a registration form containing chosen key parameters and patients filling in a validated questionnaire. RESULTS: The majority (91%) of the 619 visits was planned, and 75% of all visits included either tumor or treatment-related problems. Suspicion of recurrent disease led to further diagnostic work-up in 80 visits (13%). A total of 29 recurrences were found, and of these seven (25%) were asymptomatic, i.e. the "number needed to see" to detect one asymptomatic recurrence was 99. Treatment-related normal-tissue problems were addressed in 72% of all visits, and among these 18% required intervention. Although the majority of problems (either suspicion of recurrent disease or late effects) occurred within a few years after treatment, 39% of patients seen after three years also had problems. The majority of patients (97%) expressed satisfaction with the planned follow-up. CONCLUSION: Only few relapses are found in asymptomatic patients at routine follow-up, with one silent recurrence detected per 99 visits. However, head and neck cancer survivors have a substantial need for management of sequelae. In this context, a centralized routine follow-up may still be worthwhile.