Important Studies Flashcards
Why is initial surgical resection preferred over definitive RT for initial management of OC-SCC?
Two PRT, as well as several retrospective studies, suggest LRC and OS benefit for surgical resection compared to definitive RT.
Robertson, Glasgow ( Clin Oncol 1998, PMID 9704176): PRT of 35 pts with T2-4N0-2 OC-SCC and oropharynx randomized to surgery followed by PORT (60 Gy/30 fx) versus RT alone (66 Gy/33 fx). Trial was designed to recruit 350 pts, but was closed after only 35 pts due to significantly worse OS with RT alone. MFU was 23 months. OS significantly better with surgery and PORT (relative death rate 0.24, p = .001). Duration of LC was significantly decreased with RT alone ( p = .037). Conclusion: Defi nitive RT is sub-optimal for oral cavity cancer.
Iyer, Singapore ( Cancer 2015, PMID 25639864): PRT of 119 pts with Stage III-IV H&N squamous cell carcinoma randomized to surgery followed by PORT versus concurrent CHT and RT. MFU was 13 years. There was no significant difference in OS for entire cohort (45% vs. 35%; p = .262) and DSS (56% vs. 46%; p = .637) at 5 years for surgery versus RT alone, respectively. For pts with OC-SCC, surgery up front significantly improved 5-yr OS (68% vs. 12%; p = .038). Conclusion: OS and DSS are significantly improved with surgery and PORT compared to RT alone for OC-SCC, but not for other sites of H&N.
Is there benefit for elective neck dissection compared to neck dissection at nodal relapse?
Randomized data suggests survival benefit to up-front neck dissection compared to neck dissection at time of nodal relapse, though stage, pathologic features and location of primary should be considered.
D’Cruz, India ( NEJM 2015, PMID 26027881): PRT of 596 pts with lateralized T1-2 OC-SCC randomized to elective ipsilateral neck dissection versus therapeutic neck dissection (at time of nodal relapse). MFU was 39 months. At 3 years, elective neck dissection demonstrated significantly improved OS (80% vs. 67.5%; p = .01) and DFS (69.5% vs. 45.9%; p < .001) compared to therapeutic neck dissection. Overall rate of pathologic nodal positivity in clinically node negative neck was 30%. Rates of adverse events were 6.6% and 3.6% in elective neck dissection and therapeutic neck dissection arms, respectively. Conclusion: Ipsilateral elective neck dissection provides OS and DFS benefit in pts with early stage, well-lateralized OC-SCC, compared to therapeutic neck dissection
At what DOI should neck dissection be performed in early stage (cT1-2N0) oral tongue cancer?
Several retrospective studies have demonstrated DOI as significant predictor for locoregional recurrence. DOI ≥ 4 to 5 mm has been suggested as cutoff for neck dissection.
Huang, Princess Margaret Meta-Analysis ( Cancer 2009, PMID: 19197973): Metaanalysis of 16 studies investigated negative-predictive value of DOI from 3 to 6 mm for cT1-2N0 oral tongue cancer. Probability of lymph node positivity at time of dissection or nodal relapse after ≥ 2 years follow-up increased ≥ 5 mm DOI. There was significant increase in nodal positivity between 4 mm and 5 mm DOI ( p = .007). Conclusion: DOI strongly predicts for cervical lymph node involvement. Elective neck dissection should be considered in pts with cN0 disease with DOI >4 mm.
Ganly, MSKCC & PMH combined analysis ( Cancer 2013, PMID: 23184439): Combined analysis of 164 pts from MSKCC and PMH with pT1-2N0 oral tongue cancer treated with surgery alone (no postoperative RT). MFU was 66 months. Locoregional recurrence free survival at 5 years was 79.9%. Regional recurrence was ipsilateral in 61% of cases and contralateral in 39% of cases. Regional recurrence was 5.7% for tumors with < 4 mm DOI and 24% ≥ 4 mm DOI. Multivariate analysis demonstrated that tumor thickness ≥ 4 mm was significantly associated with regional recurrence free survival ( p = .02). Pts with regional recurrence had significantly worse disease specific survival (33% vs. 97%; p < .0001). Conclusion: Neck recurrence was significantly higher with DOI ≥ 4 mm. Contralateral neck failure was 40% in this subset of pts with early stage, cN0 disease.
What are indications and benefit for postoperative RT for OC-SCC?
What are indications and benefit for postoperative RT for OC-SCC?
What are indications and benefit for addition of CHT to postoperative RT?
The combined analysis of Bernier and Cooper (EORTC 22931 and RTOG 9501) suggests that ECE and positive margins are indications for postoperative concurrent chemoRT (See PORT for H&N cancer for details). One recent trial at Tata Memorial in India also addressed this question.
Laskar ( ASCO 2016, Abstract 6004): PRT of 900 pts with resectable OC-SCC who underwent surgery randomized to PORT alone (56– 60 Gy in 5 fx/week) (Arm A), PORT with concurrent weekly cisplatin (30 mg/m 2 ) (Arm B), or accelerated PORT (6 fx/week) (Arm C). MFU was 58 months. LRC at 5 years was 59.9% and 65.1% for Arm B versus Arm ( p = .203) and 58.2% for Arm C ( p = NS). Unplanned subset analysis demonstrated significantly improved LRC, DFS, and OS for pts with high risk features (T3-T4, N2-3, and ECE) for pts treated with standard fractionation RT and concurrent chemoRT compared to accelerated RT. Conclusion: Intensification of therapy with concurrent CHT or accelerated RT did not improve outcomes in these pts with OC-SCC. Comment: Final results are pending and oral cavity cancer may have different biology in India than in the United States.
Is there benefit to preoperative CHT, RT, or chemoRT prior to surgical resection in OC-SCC?
Several PRTs have investigated role of induction CHT with cisplatin/5-FU or TPF with no improvement in OS. Retrospective evidence suggests benefit to downstaging for pts who are unresectable.
Zhong, China ( JCO 2013, PMID 23129742): PRT of 256 pts with Stage III-IVA resectable OC-SCC randomized to two cycles of induction TPF (docetaxel 75 mg/m 2 on day 1, cisplatin 75 mg/m 2 on day 1, and 5-FU 750 mg/m 2 on days 1– 5) followed by surgery and PORT (54– 66 Gy) versus surgery followed by PORT. MFU was 30 months. Clinical response rate to induction CHT was 80.6%. There was no significant difference in OS (HR 0.977; p = .918) or DFS (HR 0.974; p = .897) with induction TPF. Pts with clinical response or favorable pathologic response ( ≤ 10% viable tumor cells) had superior OS, LRC, and distant control with induction TPF. Conclusion: There was no significant survival benefit with induction TPF.
Licitra, Italy ( JCO 2003, PMID 12525526): PRT of 195 pts with T2-4(>3 cm) N0-2 resectable OC-SCC randomized to three cycles of cisplatin and 5-FU followed by surgery versus surgery alone. PORT was included for positive margin, soft tissue invasion of face, >3 lymph nodes and/or ECE. There was no significant difference in 5-yr OS between induction CHT and surgery alone (55% vs. 55%). Fewer pts required PORT in CHT arm (33% vs. 46%). Pts who had pCR had significantly improved 10-yr OS (76% vs. 41%). Conclusion: Induction CHT does not provide survival benefit, may decrease need for PORT.
Patil, Tata Memorial, India ( Oral Oncol 2014, PMID 25130412): RR of 721 pts with Stage IV unresectable OC-SCC who received two cycles of preoperative CHT. Pts either went onto surgery followed by postoperative chemoRT, definitive chemoRT, or palliative RT. Reduction in tumor size and successful resection occurred in 43% of pts. LRC at 24 months was 20.6% for entire cohort, 32% for those who underwent surgery, and 15% for those who did not ( p = .0001). Median OS for pts who underwent surgery was 19.6 months and 8.16 months for those who did not ( p = .0001). Conclusion: Preoperative CHT improved rate of resection in pts with unresectable disease. Surgical resection was associated with significantly improved LRC and OS .
Mohr, Germany ( Int J Oral Maxillofac Surg 1994, PMID 7930766): PRT of 268 pts with T2-4N0-3 OC-SCC and oropharyngeal cancer randomized to preoperative chemoRT (36 Gy/18 fx with concurrent cisplatin) followed by surgery versus surgery alone. Surgery was completed 10 to 14 days after preoperative chemoRT. Locoregional recurrence was higher with surgery alone compared to preoperative chemoRT (31% vs. 15.6%). OS for preoperative chemoRT versus surgery alone was 19% versus 28%, respectively. Conclusion: Induction chemoRT may provide LRC and OS benefit compared to surgery alone.
What are patterns of failure after PORT?
Retrospective series have demonstrated that contralateral neck failure is common after ipsilateral neck RT and majority of failures are local, within high dose RT field.
Chan, Princess Margaret ( Oral Oncol 2013, PMID 23079695): RR of 180 pts treated with PORT for Stage I-IV OC-SCC (46% oral tongue, 23% floor of mouth, 12% hard palate, 9% buccal). MFU was 34 months. LC, LRC, and OS at 2 years was 87%, 78%, and 65%, respectively. Of 38 locoregional failures, 26 were in field. Contralateral failure occurred in three of 12 pts treated to ipsilateral neck only and more common in pts with N2b disease. Conclusion: Bilateral neck RT may be beneficial in pts with N2b disease.
Yao, University of Iowa ( IJROBP 2007, PMID 17276613): Retrospective review of 55 pts treated with IMRT for OC-SCC (49 pts received postoperative RT, five received definitive RT, and one received preoperative RT). OS and LRC at 2 years was 68% and 85%, respectively. All failures were in high dose RT field, except for one patient who failed in lower contralateral neck. Median time to locoregional recurrence was 4.1 months and locoregional control was significantly lower in pts with ECE. Conclusion: Most failures after postoperative RT are in field.
