Cancer Seventh Edition Staging Research Articles

A Descriptive Study of Quality of Life Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life (QOL). Transoral robotic surgery (TORS) has an established role in the management of early OPSCC but adjuvant treatment is often indicated postoperatively due to the high incidence of nodal metastasis associated with advanced human papillomavirus (HPV)-related OPSCC. To overcome the need for adjuvant radiation therapy (RT), neoadjuvant chemotherapy followed by TORS and neck dissection (ND) is proposed. This study aimed to assess if QOL in HPV-associated OPSCC receiving neoadjuvant chemotherapy followed by TORS and ND returns to baseline within 12 months of completing treatment. A 12 month longitudinal study was carried out at McGill University Health Centre in Montreal, Canada, among a convenience sample of patients with American Joint Committee on Cancer Seventh Edition stage III and IVa HPV-related OPSCC who were treated with neoadjuvant chemotherapy followed by TORS and ND. QOL data were obtained pretreatment and at 1, 3, 6, and 12 months following treatment completion using the European Organisation for Research and Treatment of Cancer Core and Head and Neck extension modules. Paired t tests and mixed models for repeated measures analysis were used to assess changes in QOL from baseline to 12 months postoperatively and over time, respectively. Nineteen of 23 patients (median age 58 years) who received the study treatment fulfilled the eligibility criteria. OPSCC subsites were palatine tonsil (n = 12) and base of tongue (n = 7). All 19 patients were treated per protocol and none required adjuvant RT as per pathology review and protocol requirements at a postoperative multidisciplinary team tumor board discussion. No significant differences were found when comparing 12 month QOL follow-up scores to pretreatment scores in measures that would likely be affected by RT [eg, swallowing (P = .7), social eating (P = .8), xerostomia (P = .9)]. In HPV-related OPSCC, neoadjuvant chemotherapy followed by TORS and ND as definitive treatment is associated with excellent QOL outcomes. Postoperative QOL scores returned to baseline by 3 months and were maintained for all measures, indicating a return to normal function.

Increasing Heart Dose Reduces Overall Survival in Patients Undergoing Postoperative Radiation Therapy for NSCLC

IntroductionGiven the concern for cardiopulmonary toxicity in patients with NSCLC undergoing postoperative radiation therapy (PORT), the purpose of this study was to evaluate the association between heart dose and overall survival (OS) in patients undergoing PORT with modern techniques. MethodsThis is a retrospective study of consecutive patients with NSCLC treated with PORT between May 2004 and January 2017. Clinical records were reviewed and radiation dose distributions were analyzed for association with OS. ResultsA total of 284 patients were analyzed. At the time of surgery, most patients had pathologic American Joint Committee on Cancer seventh edition stage III disease (91.2 %) and received either preoperative or adjuvant chemotherapy (92.3 %). Most patients underwent a lobectomy (81.3 %) and had R0 (80.6 %) or R1 (19.4 %) resection. PORT was delivered with a median radiation dose of 54 Gy, and 70.4 % of patients were treated with intensity-modulated radiation therapy. Dosimetric variables across a large range of doses to the heart were highly significant (p < 0.05) for OS. The volume of the heart receiving 8 Gy (HV8) was the most significant dosimetric variable (p < 0.001), and the median HV8 was 35.5 %. The median OS was 33.2 versus 53.6 months (p < 0.005) for patients with HV8 above or below 35.5 %, respectively. On multivariable analysis accounting for other potential prognostic confounders, HV8 remained highly significant (p < 0.001). ConclusionsThe data reveal a strong correlation between increasing heart dose and OS in patients with NSCLC undergoing PORT. Taken together with the recently presented LungART trial, lowering heart dose in PORT patients may help to decrease the risk of morbidity and mortality and improve the therapeutic ratio of PORT.

International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients.

Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). ON patients (≥ 80years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80years). A cytotoxic drug combination of melphalan and actinomycin-D was used. Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84years; range 80-100years). Compared with the younger cohort (n = 527; median age 67years; range 29-79years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23months (p = 0.16), overall survival was 29 versus 40months (p < 0.0001), and melanoma-specific survival was 46 versus 78months (p = 0.0007) for ON patients compared with younger patients, respectively. ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.

A single-institution, randomized, pilot study evaluating the efficacy of gabapentin and methadone for patients undergoing chemoradiation for head and neck squamous cell cancer.

The objective of the current study was to compare the safety and efficacy between 2 analgesic regimens for patients with head and neck cancer (HNC) undergoing definitive chemoradiation (CRT). The current study was a prospective, single-institution, 2-arm, randomized pilot study. Patients with American Joint Committee on Cancer seventh edition stage II to stage IV squamous cell carcinoma of the head and neck who were undergoing CRT were randomized to either arm 1, which entailed high-dose gabapentin (2700 mg daily) with the institutional standard of care (hydrocodone and/or acetaminophen progressing to fentanyl as needed), or arm 2, which comprised low-dose gabapentin (900mg daily) with methadone. The primary endpoints were safety and toxicity. Secondary endpoints were pain, opioid requirement, and quality of life (QOL). Differences between the treatment arms at multiple time points were compared using a generalized linear mixed regression model with Sidak correction. A total of 60 patients (31 in arm 1 and 29 in arm 2) were enrolled from April 2015 to August 2017. There was no difference between the treatment arms with regard to adverse events or serious adverse events. Pain was not found to be different between the treatment arms. More patients in arm 1 did not require an opioid during treatment (42% vs 7%; P=.002). Patients in arm 2 experienced significantly better QOL outcomes across multiple domains, including overall health (P=.05), physical functioning (P=.04), role functioning (P=.01), and social functioning (P=.01). High-dose prophylactic gabapentin increased the percentage of patients who required no opioid during treatment. Methadone may improve QOL compared with a regimen of short-acting opioids and fentanyl. However, pain was found to significantly worsen throughout treatment regardless of treatment arm, necessitating further studies to identify a more optimal regimen.

A Phase 1b Study of Cetuximab and BYL719 (Alpelisib) Concurrent with Intensity Modulated Radiation Therapy in Stage III-IVB Head and Neck Squamous Cell Carcinoma

Activation of the PI3K/mTOR signaling pathway is common in head and neck squamous cell carcinoma (HNSCC). BYL719 is an α-specific PI3K inhibitor that is synergistic and efficacious when combined with cetuximab, a Food and Drug Administration-approved radiosensitizing agent in the treatment of HNSCC. The agent independently has been shown to enhance radiosensitivity. This study evaluates the addition of BYL719 to cetuximab and radiation in the treatment of locally advanced HNSCC. This is a single-institution, phase 1 study. Patients with American Joint Committee on Cancer seventh edition stage III to IVB HNSCC received standard cetuximab (400 mg/m2 intravenous loading dose) before intensity modulated radiation therapy (IMRT) followed by 250 mg/m2 weekly infusions during IMRT. BYL719 was given orally during IMRT in 3 dose levels: (1) 200 mg/d, (2) 250 mg/d, or (3) 300 mg/d in a standard 3 + 3 dose-escalation design. Eleven patients were evaluable. Dose level 2 was the maximum tolerated dose for BYL719. Two patients on dose level 3 had dose-limiting toxicities of oral mucositis that required a dose reduction of BYL719. One patient on dose level 2 had a dose-limiting toxicity of nausea that led to withdrawal of on-study treatment. Related grade 3 or higher adverse events consisted of decreased lymphocyte count, oral mucositis, dysphagia, hyperglycemia, maculopapular rash, and palmar-plantar erythrodysesthesia syndrome. All 11 patients had a complete response on posttreatment imaging, and 10 remain disease free. Of the 8 patients with mutational analysis, 1 had an activating PIK3CA mutation associated with a rapid response on serial intratreatment magnetic resonance imaging scans. The recommended phase 2 dose of BYL719 is 250 mg/d in combination with cetuximab and IMRT in patients with locally advanced HNSCC. Further evaluation of the addition of BYL719 to the platinum-sparing regimen of cetuximab and IMRT in the treatment of locally advanced HNSCC is warranted.

Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for esophageal squamous cell cancer patients presenting with oligometastases.

The potential survival benefits of adding radiotherapy to systemic therapy for esophageal cancer patients with oligometastases are unknown. In this retrospective analysis, patients with stage IV esophageal cancer (according to the American Joint Committee on Cancer Seventh edition staging system) with ≤3 metastases who underwent chemotherapy with cisplatin/paclitaxel between 2012 and 2015 were identified. Patients received chemotherapy (CT) alone vs. concurrent chemoradiotherapy (CCRT) to all metastases. Of 461 patients, 97% had squamous cell cancer. One hundred and ninety-six patients (42.5%) received CCRT and 265 (57.5%) underwent CT alone. At week 8, there were 3 (1.5%) complete responses (CR) and 95 (48.5%) partial responses (PR) in the CCRT group, compared to 3 (1.1%) CR and 102 (38.5%) PR in the CT alone group. The overall rate of improvement in dysphagia score was noted in 78.5% of patients in the CCRT group versus 61.5% in the CT alone group (P=0.014). A statistically significant difference was demonstrated in disease control rate between the two groups (81.6% vs. 64.5%, P<0.001). Patients who underwent CCRT had superior median PFS and a trend toward longer median OS compared to those receiving CT alone (8.7 vs. 7.3 months, P=0.002 and 16.8 vs. 14.8 months, P=0.056, respectively). The median OS was 19.3 months in patients who achieved CR/PR, compared to 14.9 months and 9.6 months for patients who had stable disease and progressive disease, respectively (P<0.001). Compared to chemotherapy alone, chemoradiation to all sites in patients with esophageal cancer with ≤3 metastases may lead to a modest increase in PFS and a trend toward longer OS. Further investigation of optimal integration of radiotherapy and chemotherapy in these patients is warranted.

Ocular adnexal lymphoma: validation of American Joint Committee on Cancer seventh edition staging guidelines

Background/aimsTo validate the prognostic significance of the American Joint Committee on Cancer (AJCC) seventh edition staging criteria for ocular adnexal lymphoma (OAL) of all histologic subtypes.MethodsRetrospective review of clinical records...