Purpose To update the guideline recommendations on the use of larynx-preservation strategies in the treatment of laryngeal cancer. Methods An Expert Panel updated the systematic review of the ...literature for the period from January 2005 to May 2017. Results The panel confirmed that the use of a larynx-preservation approach for appropriately selected patients does not compromise survival. No larynx-preservation approach offered a survival advantage compared with total laryngectomy and adjuvant therapy as indicated. Changes were supported for the use of endoscopic surgical resection in patients with limited disease (T1, T2) and for initial total laryngectomy in patients with T4a disease or with severe pretreatment laryngeal dysfunction. New recommendations for positron emission tomography imaging for the evaluation of regional nodes after treatment and best measures for evaluating voice and swallowing function were added. Recommendations Patients with T1, T2 laryngeal cancer should be treated initially with intent to preserve the larynx by using endoscopic resection or radiation therapy, with either leading to similar outcomes. For patients with locally advanced (T3, T4) disease, organ-preservation surgery, combined chemotherapy and radiation, or radiation alone offer the potential for larynx preservation without compromising overall survival. For selected patients with extensive T3 or large T4a lesions and/or poor pretreatment laryngeal function, better survival rates and quality of life may be achieved with total laryngectomy. Patients with clinically involved regional cervical nodes (N+) who have a complete clinical and radiologic imaging response after chemoradiation do not require elective neck dissection. All patients should undergo a pretreatment baseline assessment of voice and swallowing function and receive counseling with regard to the potential impact of treatment options on voice, swallowing, and quality of life. Additional information is available at www.asco.org/head-neck-cancer-guidelines and www.asco.org/guidelineswiki .
Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma have high survival when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with ...cetuximab—an antibody against the epidermal growth factor receptor—can preserve high survival and reduce treatment toxicity is unknown. We investigated whether cetuximab would maintain a high proportion of patient survival and reduce acute and late toxicity.
RTOG 1016 was a randomised, multicentre, non-inferiority trial at 182 health-care centres in the USA and Canada. Eligibility criteria included histologically confirmed HPV-positive oropharyngeal carcinoma; American Joint Committee on Cancer 7th edition clinical categories T1–T2, N2a–N3 M0 or T3–T4, N0–N3 M0; Zubrod performance status 0 or 1; age at least 18 years; and adequate bone marrow, hepatic, and renal function. We randomly assigned patients (1:1) to receive either radiotherapy plus cetuximab or radiotherapy plus cisplatin. Randomisation was balanced by using randomly permuted blocks, and patients were stratified by T category (T1–T2 vs T3–T4), N category (N0–N2a vs N2b–N3), Zubrod performance status (0 vs 1), and tobacco smoking history (≤10 pack-years vs >10 pack-years). Patients were assigned to receive either intravenous cetuximab at a loading dose of 400 mg/m2 5–7 days before radiotherapy initiation, followed by cetuximab 250 mg/m2 weekly for seven doses (total 2150 mg/m2), or cisplatin 100 mg/m2 on days 1 and 22 of radiotherapy (total 200 mg/m2). All patients received accelerated intensity-modulated radiotherapy delivered at 70 Gy in 35 fractions over 6 weeks at six fractions per week (with two fractions given on one day, at least 6 h apart). The primary endpoint was overall survival, defined as time from randomisation to death from any cause, with non-inferiority margin 1·45. Primary analysis was based on the modified intention-to-treat approach, whereby all patients meeting eligibility criteria are included. This study is registered with ClinicalTrials.gov, number NCT01302834.
Between June 9, 2011, and July 31, 2014, 987 patients were enrolled, of whom 849 were randomly assigned to receive radiotherapy plus cetuximab (n=425) or radiotherapy plus cisplatin (n=424). 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were subsequently eligible. After median follow-up duration of 4·5 years, radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival (hazard ratio HR 1·45, one-sided 95% upper CI 1·94; p=0·5056 for non-inferiority; one-sided log-rank p=0·0163). Estimated 5-year overall survival was 77·9% (95% CI 73·4–82·5) in the cetuximab group versus 84·6% (80·6–88·6) in the cisplatin group. Progression-free survival was significantly lower in the cetuximab group compared with the cisplatin group (HR 1·72, 95% CI 1·29–2·29; p=0·0002; 5-year progression-free survival 67·3%, 95% CI 62·4–72·2 vs 78·4%, 73·8–83·0), and locoregional failure was significantly higher in the cetuximab group compared with the cisplatin group (HR 2·05, 95% CI 1·35–3·10; 5-year proportions 17·3%, 95% CI 13·7–21·4 vs 9·9%, 6·9–13·6). Proportions of acute moderate to severe toxicity (77·4%, 95% CI 73·0–81·5 vs 81·7%, 77·5–85·3; p=0·1586) and late moderate to severe toxicity (16·5%, 95% CI 12·9–20·7 vs 20·4%, 16·4–24·8; p=0·1904) were similar between the cetuximab and cisplatin groups.
For patients with HPV-positive oropharyngeal carcinoma, radiotherapy plus cetuximab showed inferior overall survival and progression-free survival compared with radiotherapy plus cisplatin. Radiotherapy plus cisplatin is the standard of care for eligible patients with HPV-positive oropharyngeal carcinoma.
National Cancer Institute USA, Eli Lilly, and The Oral Cancer Foundation.
An ASCO provisional clinical opinion offers timely clinical direction to ASCO's membership after publication or presentation of potentially practice-changing data from major studies. This provisional ...clinical opinion addresses the role of treatment deintensification in the management of p16+ oropharyngeal cancer (OPC).
For patients with p16+ OPC, current treatment approaches are well established. In the good-prognosis subset of nonsmoking p16+ patients with early-stage disease, these treatments have been highly successful, albeit with significant associated acute and late toxicity. Deintensification of surgical, radiation, and medical treatment in an effort to reduce toxicity while preserving high survival rates is an appropriate therapeutic objective currently being explored in patients who are experiencing the best treatment results. However, careful delineation of this good-risk subset is essential. While the current eighth edition of the American Joint Committee on Cancer staging system is prognostically robust, it should not be interpreted as reason to alter therapeutic decisions or justify treatment deintensification. The development of transoral surgical techniques and the adoption of intensity-modulated radiation therapy planning have been transformative in disease management and suggest potentially beneficial approaches. Recent advances in systemic treatments have been notable. The optimal integration and modification of these modalities to ameliorate toxicity has not been defined and remains an important focus of current investigation.
The hypothesis that de-escalation of treatment intensity for patients with p16+ OPC can reduce long-term toxicity without compromising survival is compelling and necessitates careful study and the analysis of well-designed clinical trials before changing current treatment standards. Treatment deintensification for these patients should only be undertaken in a clinical trial. Additional information is available at www.asco.org/head-neck-cancer-guidelines .
To present evidence-based guidelines for the treatment of oropharyngeal squamous cell carcinoma (OPSCC) with definitive or adjuvant radiation therapy (RT).
The American Society for Radiation Oncology ...convened the OPSCC Guideline Panel to perform a systematic literature review investigating the following key questions: (1) When is it appropriate to add systemic therapy to definitive RT in the treatment of OPSCC? (2) When is it appropriate to deliver postoperative RT with and without systemic therapy following primary surgery for OPSCC? (3) When is it appropriate to use induction chemotherapy in the treatment of OPSCC? (4) What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC?
Patients with stage IV and stage T3 N0-1 OPSCC treated with definitive RT should receive concurrent high-dose intermittent cisplatin. Patients receiving adjuvant RT following surgical resection for positive surgical margins or extracapsular extension should be treated with concurrent high-dose intermittent cisplatin, and individuals with these risk factors who are intolerant of cisplatin should not routinely receive adjuvant concurrent systemic therapy. Induction chemotherapy should not be routinely delivered to patients with OPSCC. For patients with stage IV and stage T3 N0-1 OPSCC ineligible for concurrent chemoradiation therapy, altered fractionation RT should be used.
The successful management of OPSCC requires the collaboration of radiation, medical, and surgical oncologists. When high-level data are absent for clinical decision-making, treatment recommendations should incorporate patient values and preferences to arrive at the optimal therapeutic approach.
Biology and Management of Salivary Gland Cancers Adelstein, David J., MD; Koyfman, Shlomo A., MD; El-Naggar, Adel K., MD, PhD ...
Seminars in radiation oncology,
07/2012, Letnik:
22, Številka:
3
Journal Article
Recenzirano
The salivary gland cancers are uncommon neoplasms of the head and neck, which exhibit considerable pathologic, biological, and clinical diversity. Surgical resection, often with postoperative ...radiation, is the standard therapeutic approach, and the results after treatment vary widely depending on the tumor histology. Chemotherapy has been of only limited palliative benefit in patients with advanced disease, and there has been little exploration of its use in definitive management. Recent investigation has focused on identification of the characteristic molecular signatures and genomic alterations of the specific histologic subtypes. These efforts have suggested the potential for molecularly targeted therapies, and clinical trials exploring this approach are currently underway.
The Head and Neck Intergroup conducted a phase III randomized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer.
Eligible ...patients were randomly assigned between arm A (the control), single daily fractionated radiation (70 Gy at 2 Gy/d); arm B, identical radiation therapy with concurrent bolus cisplatin, given on days 1, 22, and 43; and arm C, a split course of single daily fractionated radiation and three cycles of concurrent infusional fluorouracil and bolus cisplatin chemotherapy, 30 Gy given with the first cycle and 30 to 40 Gy given with the third cycle. Surgical resection was encouraged if possible after the second chemotherapy cycle on arm C and, if necessary, as salvage therapy on all three treatment arms. Survival data were compared between each experimental arm and the control arm using a one-sided log-rank test.
Between 1992 and 1999, 295 patients were entered on this trial. This did not meet the accrual goal of 362 patients and resulted in premature study closure. Grade 3 or worse toxicity occurred in 52% of patients enrolled in arm A, compared with 89% enrolled in arm B (P <.0001) and 77% enrolled in arm C (P <.001). With a median follow-up of 41 months, the 3-year projected overall survival for patients enrolled in arm A is 23%, compared with 37% for arm B (P =.014) and 27% for arm C (P = not significant).
The addition of concurrent high-dose, single-agent cisplatin to conventional single daily fractionated radiation significantly improves survival, although it also increases toxicity. The loss of efficacy resulting from split-course radiation was not offset by either multiagent chemotherapy or the possibility of midcourse surgery.
Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy in oropharyngeal squamous cell carcinoma (OPSCC) that was determined to be ...relevant to the American Society of Clinical Oncology (ASCO) membership. After applying standard critical appraisal policy and endorsement procedures, ASCO chose to endorse the ASTRO guideline. Methods The ASTRO guideline was reviewed by ASCO content experts for clinical accuracy and by ASCO methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations. The ASCO guideline approval body, the Clinical Practice Guidelines Committee, approved the final endorsement. Results The ASCO Expert Panel determined that the ASTRO guideline recommendations, published in July 2017, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the ASTRO guideline and added minor qualifying statements. Recommendations Recommendations for the addition of systemic therapy to definitive radiotherapy in the treatment of OPSCC, postoperative radiotherapy with and without systemic therapy following primary surgery of OPSCC, induction chemotherapy in the treatment of OPSCC, and the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC are outlined for a variety of disease stages and clinical scenarios. ASCO Endorsement Panel qualifying statements and minor modifications were made to the ASTRO recommendations. The staging system that is referenced in these guidelines is the American Joint Committee on Cancer Staging Manual, 7th edition. Additional information is available at: www.asco.org/head-neck-cancer-guidelines and www.asco.org/guidelineswiki .
Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with ...radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.
Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility ...required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy.
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