Rethinking TNM staging in head and neck cancer: when limited metastatic disease should not preclude curative local treatment.

Acinar cell carcinoma of the pancreas: is resection justified even in limited metastatic disease?

Salivary micro RNAs as Potential Biomarkers for Oral and Head and Neck Cancers

Definitive Radiation Therapy with Chemotherapy for Stage IV Anal Cancer: A National Cancer Database Analysis

Imatinib for palliative and adjuvant treatment of gastrointestinal stromal tumours (GISTs) with common KIT mutations has been revolutionary. For patients with locally advanced, limited metastatic or recurrent disease, neoadjuvant imatinib may downstage the tumour, enabling surgery with curative intent; however, the optimal duration of neoadjuvant imatinib is unknown. We conducted a retrospective review of patients with locally advanced, limited metastatic and recurrent GIST treated with neoadjuvant imatinib prior to consideration of surgical resection in the period 2012-2024 at three cancer centres in NSW, Australia. Baseline and outcome data were collected. The primary endpoint was the progression-free survival (PFS). A total of 30 patients were identified with 38 instances of primary locally advanced, recurrent or limited metastatic disease. The median per-patient duration of neoadjuvant imatinib was 7.8 months (range 2.9-14.9 months), and the median per-episode duration of neoadjuvant imatinib was 9.1 months (range 3.0-27.4 months). Maximum radiological response was achieved at 3.8 months for primary tumours and 6.7 months for recurrent tumours. Partial response occurred in 77% and progression in 0%. Of the 25 patients with available data, 96% were symptomatic, and 89% reported early symptomatic benefit from imatinib within 1 month. Complete surgical resection occurred in 58% of all episodes of neoadjuvant treatment. The estimated PFS rates at 2 and 5 years were 84% and 55% respectively. Overall survival rates were 84% at both 2 and 5 years. Neoadjuvant imatinib provided effective symptomatic and radiological responses in patients with locally advanced, limited metastatic or recurrent GIST. A duration of 3-6 months treatment for primary tumours and 6-12 months for recurrent disease appears sufficient for most patients. Mutational profile analysis is of particular value for patients who do not have early symptomatic benefit, have poor radiological response or have recurrent disease.

The bone scan patterns of benign and malignant uptake in 432 patients with newly diagnosed prostate carcinoma were reviewed in relation to prostate-specific antigen (PSA) levels determined within 4 months of scintigraphy. Scan results were categorized in terms of likelihood of metastatic disease and anatomical locations of benign and malignant lesions were tabulated. At least one suspect focus was identified in 138 scans (32%), and metastatic bone disease was present in 38 (9%). Metastatic disease prevalence increased from 1% for PSA <20 ng x ml(-1) to 58% for PSA>100 ng x ml(-1). Among patients with PSA>20 ng x ml(-1) (n = 157), 70 (45%) had at least one bone scan finding of concern for metastases and 35 (22%) proved to have metastatic disease. Almost all scans with metastases had either limited disease (< or = 5 suspicious lesions; n = 16; 42%) or extensive metastases (> 20 abnormalities; n = 19; 50%). The majority of patients with limited skeletal metastases had PSA < 100 ng x ml(-1) (11/16; 69%), while almost all patients with extensive skeletal involvement had PSA >100 ng x ml(-1) (17/19; 89%). Among those with limited metastatic disease, most (13/16; 81%) had at least one lesion in the pelvis or sacrum; the next most common sites were in the thoracic and lumbar spine (six each; 38%). In scans with a low to moderate suspicion for bone metastases, the only anatomical site with a significantly higher prevalence of malignant than benign lesions was the pelvis.

Clinical Features of Patients With Second Primary Lung Cancer After Head and Neck Cancer

BackgroundOur objective was to evaluate the outcomes of metastatic head and neck squamous cell carcinoma (HNSCC) by disease burden with an emphasis on metastasis-directed therapy (MDT) in patients with limited metastatic disease burden.MethodsIn total, 186 patients who developed metastatic disease after definitive therapy for HNSCC were included. Clinically and radiographically apparent metastases were enumerated. Kaplan–Meier methods were used to estimate survival. Cox regression was used to assess the association between clinical variables.ResultsPatients with a single metastasis had a 5-year overall survival (OS) of 35% (95% CI 16–54%) in contrast to patients with multiple metastases with a 5-year OS of 4% (95% CI 2–9%). Thirty patients (16.1%) underwent MDT. On multivariable analysis, oral cavity or sinonasal primary (HR 2.22 95% CI 1.16–4.25, p = 0.015; HR 4.88, 95% CI 1.10–21.70, p = 0.037, respectively) were associated with higher risk of death, whereas receipt of MDT (HR 0.36, 95% CI 0.17–0.74, p = 0.006) was associated with lower hazard of death. Median subsequent metastasis-free survival and 5-year survival after MDT (n = 30) were estimated at 26.4 months (95% CI: 9.8–54.0) and 31%, (95% CI: 15–48%).ConclusionsHNSCC patients with limited metastatic disease may derive significant benefit from MDT. Prospective trials evaluating MDT in HNSCC are warranted.

Around 5-8 per cent of women diagnosed with cervical cancer present with metastatic disease at presentation and 16-25 per cent of patients fail at either within irradiated fields or at distant sites post-curative therapy in advanced cervical cancers. Conventionally, chemotherapy with palliative intent constituted the mainstay of treatment with modest survival outcomes and radiation therapy was reserved for symptomatic benefit only. While targeted therapies and immunotherapy have been added in therapeutic armamentarium, the impact on the outcomes is modest. In limited metastatic disease, radiation therapy to metastatic sites from different primary cancers has shown survival benefits; however, the data are scarce in cervical cancer. With a better understanding of the molecular biology of the metastases and recurrence pattern, emphasis is laid upon total eradication of the disease rather than offering relief from symptoms. This article summarizes the role of radiation therapy in limited metastatic disease and recurrent cervical cancer.

Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. The primary end point was overall survival. In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. clinicaltrials.gov identifier: NCT00849615.

Supraomohyoid neck dissection

Importance: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. Objective: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. Design, Setting, and Participants: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. Interventions: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. Main Outcomes and Measures: The primary end point was overall survival. Results: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients, 45%), liver involvement (11, 18.3%), lung involvement (10, 16.7%), localized peritoneal involvement (4, 6.7%), or other (8, 13.3%) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < 0 .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. Conclusions and Relevance: Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. Trial Registration: clinicaltrials.gov identifier: NCT00849615.

Oligometastatic colorectal cancer (CRC), characterised by limited metastatic disease, has traditionally been managed with surgery and chemotherapy. However, advances in stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy (SBRT), have introduced the possibility of curative outcomes for selected patients with limited metastatic disease. SABR delivers high-dose, highly precise radiation with minimal toxicity, making it an attractive alternative or complement to surgery and systemic therapy. This narrative review evaluates the role of SABR in the management of oligometastatic CRC, and its application in both palliative and curative settings. A systematic search of PubMed and Scopus databases (2014-2024) was conducted using search terms including "colorectal cancer", "oligometastatic", "SABR", "SBRT", "palliative", and "radical". Relevant meta-analyses, systematic reviews, and single- and double-arm studies were included. SABR demonstrates promising outcomes in both palliative and curative settings for oligometastatic CRC. Trials like SABR-COMET report significant improvements in overall survival (OS) and progression-free survival (PFS) with SABR, achieving a median OS of 50 months compared to 28 months with standard care. SABR is particularly effective for pulmonary metastases, achieving higher local control (LC) rates than hepatic lesions, likely due to differences in tissue radiosensitivity. Palliative SABR has been shown to delay systemic therapy and improve symptom management, with low toxicity rates, while radical SABR offers durable disease control and potential curative outcomes. Despite these benefits, evidence is limited by small cohort sizes, variable dosing regimens, and a lack of CRC-specific randomised trials. SABR has emerged as a transformative treatment for oligometastatic CRC, providing significant benefits in both palliative and curative settings, although not yet outperforming traditional treatment modalities such as surgery. Future research, including ongoing phase III trials, aims to refine patient selection, optimise dosing protocols, and integrate SABR with systemic treatments to enhance outcomes. With further validation, SABR has the potential to redefine the therapeutic landscape for oligometastatic CRC, offering hope for improved survival and quality of life.

Long-Term Follow-Up of Patients with Metastatic Epidural Spinal Cord Compression from Breast Cancer Treated with Surgery Followed by Radiotherapy.

Patients with head and neck cancer (HNC) experience increased risk of depression and compromised quality of life. Identifying patients with HNC at risk of depression can help establish targeted interventions. To identify factors that may be associated with the development of moderate or severe depression during treatment of HNC. This is a retrospective, ad hoc, secondary analysis of prospectively collected data from a randomized, double-blind, placebo-controlled clinical trial. Patients were screened at academic- and community-based tertiary care HNC centers from January 2008 to December 2011. Of the 125 evaluable patients with stages II through IV HNC but without baseline depression, 60 were randomized to prophylactic antidepressant escitalopram oxalate and 65 to placebo at the time of the initial diagnosis. Data analyses were conducted from May 2016 to April 2017. Depression outcomes were measured using Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) scores (range, 0-27 with a score of 11 or higher indicative of moderate or greater depression). Factors that may be associated with development of moderate or severe depression were assessed, including patient demographics; cancer site and stage; primary treatment modality (surgery or radiotherapy); history of depression or other psychiatric diagnosis; previous treatment of depression or suicide attempt, family history of depression, suicide, or suicide attempt; and baseline score on the QIDS-SR and clinician-rated QIDS instruments. Participants were stratified by study site, sex, cancer stage (early [stage II] vs advanced [stage III or IV]), primary modality of treatment (radiotherapy with or without chemotherapy vs surgery with or without radiotherapy), and randomization to placebo or escitalopram and balanced within these strata. The mean (SD) age of the 148 patients in the study population was 63.0 (11.9) years; 118 (79.7%) were men, and 143 (96.6%) were white. In the evaluable population of 125 patients, receiver operating characteristic analyses assessing the area under the curve for baseline QIDS-SR score (0.816; 95% CI, 0.696-0.935) and for initial radiotherapy-based treatment (0.681, 95% CI, 0.552-0.811) suggested that these 2 variables were associated with the likelihood of developing moderate or greater depression during the study period among patients who did not receive prophylactic antidepressants. The diagnostic sensitivity for identifying patients at risk of depression using the baseline QIDS-SR score improved to 100% at a threshold of 2 from 94% at a threshold of 4. Baseline symptoms and initial radiotherapy-based treatment may be associated with development of moderate or greater depression in patients with HNC. Patients with QIDS-SR baseline scores of 2 or higher may benefit the most from pharmacologic prophylaxis of depression.

e12054 Background: Late sequelae of breast cancer therapies potentially impact morbidity and mortality with increasing numbers of survivors. Radiation exposure has been linked to increased incidence of second primary cancers (SPC). However, to date, there is limited literature describing incidence of head and neck (HN) and esophageal cancers in patients with an index breast cancer (BC). This study aimed to describe the incidence of esophageal and HN cancers following breast cancer diagnosis. Methods: Standardized incidence ratios (SIRs) were calculated using the Surveillance, Epidemiology, and End Results (SEER) 9 database for BC patients diagnosed from 1973-2013. SIRs compared incidence of HN and esophageal cancer after an initial BC diagnosis to the general population. HN included oral cavity, pharynx, and larynx. BC patients were grouped into those who received radiotherapy for their breast cancer (n = 216,045) and those who did not (n = 289,596). SIRs were calculated in 5-year intervals. SEER does not contain information on chemotherapy. Results: Less than 1% of BC patients developed HN (0.3%) or esophageal cancers (0.1%), irrespective of radiation treatment. However, among patients with an index BC who received radiation therapy, there was significant but small increased incidence of HN and esophageal cancers five to nine years following treatment (HN SIR: 1.22; 95% CI, 1.04-1.43 and esophagus SIR: 1.44; 95% CI, 1.09-1.87). Esophageal cancer incidence continued to increase through 15 years of follow-up, however incidence of HN was not significant beyond ten years after the index BC diagnosis and radiation treatment. Conclusions: Compared to the general population, breast cancer patients have elevated incidence of HN and esophageal cancers detected five to nine years after receiving radiation treatment, but only the incidence of second primary esophageal cancer remains elevated at 15 years. These findings warrant further investigations of breast cancer radiation and future malignancies.