DR zerubabel oncology resident TASH

1. Locally advanced oral cavity SCC
Presenter Dr. Zerubbabel. A ( R2)
Moderator: Dr. Edom.S (consultant
Oncologist)

2. Contents of the Presentation
Case presentation
Introduction
Clinical manifestations
Diagnostic and staging workup
Staging
Management
Follow-up/ surveillance
Case critics
References

3. The case
 A 60 year old male patient presented with a complaint of left buccal mucosa
swelling of 02 years duration which subsequently got ulcerated.
 He is also a known RVI patient on HAART for the past 9 years with recent CD4
count of 700 before 04 months
 He is a know hypertensive patient for the past 05 years on antihypertensive and
diagnosed to have type 2 DM before a year and now he is on insulin.
 He has history of smoking 03 pack years, along with alcohol use and Kchat
chewing for many years

4. Investigations
 Head and neck CT scan:
 Left buccal mucosa enhancing mass measuring 2.4 *1.6 cm
 Centrally necrotic left level IB LAP measuring 2.1 * 2 cm,
 Left level IIA LAP measuring 2.4 * 2.1 cm
 After re-evaluation it was known that it has Left mandibular involvement and
staged as cT4N2M0 ( stage IV A)
 CXR ====normal
 Abdominal U/s ===== normal
 Biopsy = keratinizing squamous cell carcinoma

9. The case
 He completed phase I RT (44 Gy, 22#), before 5 days
 Opposed lateral fields with a filed size of 14.1 cm * 10.7 cm
 Lower cervical AP field with a filed size of 20 cm * 11.4 cm
 SSD ==========80 cm
 Position ====== supine
 No beam weighting done
 No concurrent chemotherapy given

14. Question……???

15. Introduction…..
 Oral cavity cancer accounts for about 30 % of all H & N cancers, 3 - 4 % of all cancers
worldwide
 In the year 2018 an estimated 320,000 new cases and about 150,000 deaths were
reported worldwide, attributable to oral cavity cancer
 90% of oral cavity cancer are well to moderately differentiated squamous cell
carcinoma
 Males have a higher incidence than females, with a ratio of 3:2.
 Has a strong causal relationship with tobacco and alcohol use
 In South Asia, it is highly prevalent and accounts for 17% of all malignancies in India
compared to less than 5% in Western countries.
 The chewing of betel nut leaves mixed with tobacco is thought to be a leading cause
of oral cavity cancers in South Asian countries

17. Clinical manifestation
 The natural history and clinical presentation of primary carcinomas located in each
subsite of the oral cavity vary significantly
 The clinical presentation also varies significantly with histologic type, and stage of
the tumor
 Many patients with oral cavity tumors present with advanced-stage disease as
initial symptoms may be vague and painless.
 The area has a rich lymphatic supply, and initial regional node dissemination is to
nodal groups at levels I to III.
 Tumors at or reaching to the midline drains bilaterally
 Rate of skip metastasis is common with oral tongue tumors
 Regional node involvement at presentation is evident in about 30 – 40 % of
patients, but the risk varies according to subsite.

18. Tumor subsite Overt metastasis Occult nodal disease
Lip 5 – 10 % 5 – 10 %
Oral tongue 35 – 40 % 32 %
FOM 30 % 26 %
Buccal mucosa 9 – 31 % 16 %
Upper gingiva 16 % 18 %
Lower gingiva 21 %
RMT 39 % 25 %
 Rate of overt and occult LN involvement in patients with
locally advanced oral cavity cancers by sub site ( for T3/T4
diseases)
 deep mucosal invasion, higher T-stage, perineural invasion, infiltrative type , and poorly
differentiated tumors have been correlated with a higher incidence of lymph nodal
involvement

20.  Patterns of lymph node involvement from squamous cell
carcinoma of the buccal mucosa.

21. Approach to the patient
Comprehensive history and physical examination.
The history of present illness should address the following issues:
- tobacco and alcohol use;
- dysphagia; odynophagia
- trismus and pain
- difficulties with speech; hoarseness
- loose teeth; ill-fitting dentures
- hypoesthesia of the face, lips, or mandible
- weight loss; and malnutrition.

22. Cont’d
Detailed visual and digital examinations are particularly important
Palpation of the oral cavity can help assess bony involvement, tongue fixation,
and depth of involvement.
Deviation or fixation of the tongue suggests involvement of extrinsic muscles of
the tongue.
Bimanual palpation can help assess the depth of tumor invasion into
musculature of the tongue and floor of the mouth.
A thorough palpation of the neck is important to assess regional nodal disease.
A multidisciplinary approach of evaluation should be implemented.
A biopsy of the primary lesion and FNA from the neck nodes

23. Imaging
 CT Scan determine the local extent of the disease
- extent of soft tissue invasion
- asses bony involvement and
- occult disease in the neck nodes
 MRI more accurately predicts
- soft tissue invasion
- depth of invasion
- perineural spread in oral tongue cancers
 MRI can be used safely in
- patients who has significant dental artifact that obscures
visualization of the primary tumor on CT
- contrast allergic patients
- lesion that is not well visualized on CT.

24. Imaging
 Panoramic X ray
 A chest x-ray should be performed to exclude lung metastases or a second
primary cancer
 Ultrasound may be used to screen for enlarged lymph nodes that are not
clinically detectable.
 In experienced hands, the accuracy of ultrasound when combined with
fine-needle aspiration may be superior to CT or MRI for staging the neck

25. Staging
The eighth edition of the AJCC Staging Manual

26. The eighth edition of the AJCC Staging Manual

27. Group/prognostic staging
The eighth edition of the AJCC Staging Manual

28. Treatment
 The aim of treatment
- Optimal rates of cure
- Where cure is not feasible every attempt
should be made to provide loco-regional
disease control.
- Preservation or restoration of form and function.

29. MDT Evaluation
Head and neck surgical oncology
Radiation and medical oncology
Nursing and dietary
Speech – language/
swallowing therapist
Dentistry and Plastic
surgery
Social worker
Multidisciplinary team involvement is particularly important for Oral cavity ca ,
because critical physiologic functions may be affected such as mastication,
deglutition, and articulation of speech.

30. Pre-treatment dental evaluation
 A complete dental examination should be performed on all patients, whether
dentate or edentulous, before irradiating any portion of the mandible or
maxilla
 ORN: Teeth with high-risk dental factors specifically, those teeth that will
reside within the high-dose radiation volume which demonstrate significant
periodontal disease or advanced caries, or are otherwise in a state of disrepair
should be extracted before initiation of RT
 Once RT is initiated high risk teeth should be removed before the patient
receives doses of more than 55 Gy
 A healing time of 14 to 21 days is recommended after extraction, before
initiating radiation therapy

31. Treatment
 Effective management lies on successful management of primary tumor as
well as regional lymphatic
 Combined modality treatment is the current standard of care for patients
with locally advanced SCC as single modality therapy has inferior outcome
 Surgical Resection
 Radiation
 CCRT
 The specific treatment is dictated by the TN stage and, if cN0 at diagnosis, by
the risk of nodal involvement

32. Factors affecting Rx choices
Tumor factors
Site and laterality
Size /stage of the tumor
Depth of invasion
Tumor grade
Patient factors
Performance status
Age
Previous treatment
Presence of comorbidity

33. Cont’d
Treatment of the primary tumor
Treatment of the neck

34. Surgical Resection
 Surgery is generally recommended as the initial therapy for locally advanced
oral cavity cancers.
Trans-oral approach
Trans-cervical approach
Mandibulectomy
 The primary objectives are
- complete resection of the primary tumor with negative margins
- staging and treatment of the regional lymphatics

35. Cont’d
 In most cases, simultaneous resection and reconstruction is feasible with
acceptable functional outcomes.
 Every attempt should be made to ensure negative resection margins
 Positive margins are associated with a worse prognosis, so whenever
feasible, re-resection of any positive margin is preferred
 Margin status is one of the most important variables associated with
survival.
- locoregional control is significantly improved with margins of
5mm or greater, relative to margins of < 5mm
 Close margins, typically defined as less than 5 mm, may also portend a
worse prognosis

37. Treatment of the neck
 Dictated by the extent and the site of the tumor at initial tumor staging
 Depth of mucosal invasion Vs laterality /extent of the primary tumor
 The depth of tumor invasion has been reported to be the best predictor for regional
metastasis in the cN0 neck.
 END should be done based on at least a 20% probability of occult nodal disease being
present for tumors that are cN0
 A meta-analysis identified a depth of invasion of 4 mm from the mucosal surface in oral
tongue cancers as the cutoff most frequently cited as an indication for END, based on a
NPV of 95.5%.
 Tumor on the FOM may need END with a 1.5 depth of mucosal invasion.
 The current recommendation is , with a depth of invasion > 4 mm, END should be strongly
considered if RT is not already planned.

38. Treatment of the neck
 Therapeutic neck dissection ( TND)
- Clinically node positive neck ( cN+ve)
 Elective neck dissection ( END)
- Clinically node negative neck (cN0 disease)
- Elective dissections are generally selective, preserving all major structures, unless
operative findings dictate otherwise
 Whether END or TND, it should be done at the same time as part of treatment of
the primary tumor
 SLNB
 Observation followed by TND
 RT
- Therapeutic neck radiation (TNR)
- Elective node irradiation (ENR)
 ENI and END are equally effective in the management of the cN0 neck, with
control rates exceeding 90%

40. Types of neck dissection
 Radical neck dissection (comprehensive neck dissection)
- removes may structures in the neck/ extensive dissection
 MRND/modified comprehensive neck dissection/ or functional neck dissection
- preserve structures not involved with cancer
- remove only structures involved by the tumor, fat, fascia, and lymph nodes.
 There are three types of MRND:
- type I = cranial nerve (CN) XI is spared
- type II = CN XI and the internal jugular vein are spared
- type III (functional) = CN XI, the internal jugular vein, and the
sternocleidomastoid muscle are spared.

41. Selective Node Dissection
 A more limited form of procedure with removal of LN levels that are at
greatest risk for nodal metastatic spread.
 Supported with data demonstrating that regional control and survival
rates do not decrease, particularly when adjuvant therapies are used to
manage microscopic residual disease in high-risk patients
 SND is denoted by the lymph node levels removed (e.g., SND II to IV).
 Recommended for
- the cN0 neck,
- for selected clinically positive necks (mobile, 1- 3 cm lymph nodes)
- for removing residual disease after RT/CCRT when there has been
excellent regression of N2 or N3 disease

42. Therapeutic Node Dissection
 Done for involved cervical LNs
- about 75 % pathologically positive
- up to 15.8% skip metastasis to level III or IV
 For patients with a cN-positive neck, a SND at levels I to IV or I to V is
recommended.
 The use of MRND is typically reserved for patients with
- advanced nodal disease (N3),
- disease extending into level V LNs
- invading critical structures in the neck.

43. Surgery with RT Vs RT alone
 Robertson et al. conducted a phase III study in the UK of 35 patients with T2–
T4/N0–N2 oral cavity or oropharyngeal cancers comparing surgery and
postoperative radiation versus radiation alone.
 The study was closed early (of the anticipated 350 patients only 35 patients
were enrolled ) because a difference in survival was identified
 An interim analysis done after accrual of 30 patients revealed a highly
significant survival advantage for patients in the combination arm (12 deaths
out of 15 patients in the RT alone arm versus 2 deaths out of 15 patients in
the combination arm (P = 0.0006), stratifying for performance status).
 After 23 months, LRC, OS, and CSS, were all improved in the surgery plus
radiation arm. ( P value for OS = 0.001)

44. Peters LJ. et al …………….( MDACC)
 A phase III prospective, randomized trial designed to determine the optimal dose of
conventionally fractionated PORT for advanced head and neck cancer in relation to
clinical and pathologic risk factors
 Patients ( N = 264) who underwent primary surgery for AJCC stage III or IV SCC of
the oral cavity, oropharynx, hypopharynx, or larynx and who required PORT were
eligible.
 Dose-response relationship for PORT and pathologic risk groups in head and neck
cancer
 The sites in the high-risk group --------- 63 Gy or 68.4 Gy
low risk sites ----------------57.6 Gy or 63 % Gy, all at 1.8 Gy per fraction.
 The concept of “treatment package time”/ TPT was introduced to define the interval
from surgery to the completion of PORT

45. Cont’d
 With daily # of 1.8 Gy, a minimum dose of 57.6 Gy should be given to the operative
bed ……..and up to 63 Gy be given to sites of increased risk, especially regions of the
neck with ENE
 Dose escalation above 63 Gy at 1.8 Gy per day does not appear to improve the
therapeutic ratio
 Margin status and ENE were the only independent tumor-related risk factors
predicting LRC and OS
 TPT cutoff of 85 days was also identified as predictor of LRC, CSS, and OS which
showed its highest impact at the lowest dose level (< 60 Gy)

46. RT Vs CCRT, Postoperatively
 A combined analysis of data from two randomized landmark studies RTOG
9501 and EORTC 22931 demonstrated improved LRC and DFS rates with
chemoradiation ( cisplatin 100 mg m2 on days 1, 22, and 43) compared to
PORT alone.
 The two trials had differing eligibility criteria, but a comparative analysis
by Bernier et al. showed that all patients with positive margins and/or
extranodal extension derived the greatest benefit from postoperative
chemoradiation
 RTOG 9501 --------------- > LRC, DFS
 EORTC 22931------------ > LRC, DFS and OS

47. EORT 22931( Bernier et al.)
 Compared RT alone Vs CCRT in the post operative setting
 334 patients with oral cavity, oropharynx, hypopharynx & larynx, ( pT3/T4 with
any N except T3N0), who underwent surgery with curative intent were
randomized into two arms ( 1:1 ratio)
 Only 26 % were patients with oral cavity cancer
1st group taking RT alone ( 66 Gy , 30 #)
2nd group taking the same dose of RT with concurrent cisplatin
 In both arms the low risk neck recived 54 Gy of RT
 Primary end point: progression free survival/ PFS

48. EORTC 22931
After a median follow-up of 60 months
 The 5 year cumulative incidence of distant metastasis was 25% vs 21% ( p = 0.61)
 The cumulative incidence of 5 yr second primary tumors were 13 % vs 12 % ( p = 0.83)
 The CCRT group showed high rate of acute toxicities but there was no significant difference
in the rate of late complications
EORTC 22931 RT ( n= 167) CCRT ( n= 167) P value
Median PFS 23 months 55 months 0.04
3 yr DFS 41 % 59 % 0.009
5 yr PFS 36 % 47 % 0.04
3 yr OS 49 % 65 % 0.02
5 yr OS 40 % 53 % 0.04
5 yr LRC 69 % 82 % 0.007
5 yr LRR 31 % 18 % 0.07

50. RTOG 9501
 After undergoing total resection of all visible and palpable disease, 459 patients were enrolled
into two groups:
- 231 patients were assigned to receive RT alone ( 60 – 66 Gy)
- 228 patients received same dose of RT with concurrent cisplatin
 Only 27 % were patients with oral cavity cancer
 Primary end point = Loco-regional control, secondary end points were DFS & OS
 After a median follow-up of 45.9 months
 overall survival didn’t show any significant difference among the treatment groups
RTOG 95_01 RT (n = 231) CCRT (n = 228) P value
2 year DFS 43 % 54 % 0.04
2 year LRC 72 % 82 % 0.01
LRF 30 % 19 % 0.01
OS 57 % 63 % 0.19
G 3&4 toxocity 34 % 77 %

52. RTOG 9501
10 year update
 Unplanned analysis of subset of those patients with positive surgical margin and/or
ENE the revealed a different result
 In the analysis of all randomized eligible patients there was no significant difference in
all the tumor outcomes assessed.
 With long time of follow-up the differences initially observed were narrowed
 Subgroup analysis of those who had either microscopically involved margins and /or
ENE showed improved LRC and DFS with CCRT
PSM/ENE RT alone CCRT p value
LRF 33.1 % 21 % 0.01
DFS 12.3 % 18.4 % 0.05
OS 19.6 % 27.1 % 0.07
RTOG 9501 RT CCRT p value
LRF 28.8 % 22.3 % 0.1
DFS 19.1 % 20.1 % 0.25
OS 27 % 29.1 % 0.31

54. Indications for Chemoradiotherapy
 The impact of chemoradiotherapy appears to be most pronounced in patients with
Extranodal extension
Positive surgical margins
 Indications for postoperative radiotherapy ( PORT)
Close/ uncertain resection margins
Perinueural invasion
Lypmphovascular space invasion
Multiple positive LNs
Unknown LN status
 Preferred interval between resection and postoperative RT is ≤6 weeks

55. Treatment Delay ( TPT)
 It is well appreciated that head and neck tumors are rapidly proliferating.
 A multi-institutional prospective study by Ang et al. demonstrated that
the total treatment time from the completion of surgery to the
completion of radiation may affect the likelihood of ultimate disease
control.
 This study illustrated the impact of overall treatment time on 5-year LRC
rate
 The rate of LRC at 5 years for
TPT < 11 weeks = 76%,
TPT 11 - 13 weeks = 62%
TPT >13 weeks = 38%
 Hence, it is recommended that adjuvant radiation proceed as soon as
surgical wounds are well healed, optimally 4 to 6 weeks after completion

56. Induction chemotherapy
 Generally not recommended in the standard management of resectable oral cavity
SCC.
 For down staging tumors and enabling radical surgery
 Technically unresectable oral cavity SCC ( T4a, T4b)
 The balance b/n the extent of surgery required to achieve negative margins and
acceptable cosmetic and functional impairment defines the resctability of a tumor.
 A combination of docetaxel, cisplatin, and 5-FU is the preferred induction regimen
for clinically fit patients with reported response rates of 17% to 50%

57. Induction cheomtherapy
 In a trial conducted by Licitra et al., 94 patients with resectable advanced oral
cavity SCC were randomized to
Cisplatin + 5 FU ( 2 cycles) followed by surgery or upfront surgery
--------------------------------radiation therapy was reserved for high risk patients
 Preoperative chemotherapy results in
- fewer mandibular resections
- decreased use of PORT
- there was no effect OS.
- response rates decrease with increasing stage in oral cancers
 It is strongly recommended that the selection of patients for induction
chemotherapy be made in a multidisciplinary fashion.

58. Induction Chemotherapy
 Patil MV et al. undertaken retrospective analysis of 721 patients with
technically unresectable oral cavity tumors who were treated with NACT during
the period from January 2008 - August 2012
 Who were deemed technically unresectable??...........MDT based decision
- 74 ( 10.2 %) patients = Platinum + 5 FU + Docetaxel
- 647 ( 89.2 %) patients received 2 drug regimen = platinum + taxene
 Buccal mucosa was the most common subsite (500 patients, 69.3 %)
 After 2 cycles of chemotherapy, the patients were re-evaluated in the
multidisciplinary clinic ( average number of cycles received = 2)

60. Cont’d
 Response rate was evaluable in 618 patients & the overall response rate was 25.1%
 The response rate with 3 drug regimen = 50%
2 drug regimen with docetaxel = 30.4% and with
paclitaxel = 17.2%
 Resectability was achieved in a total of 310 patients
49 patients ( 66.21 %) taking 3 drug regimens
261 patients ( 40.34 %) taking 2 drug regimen patients.
 Among patients who were resected 195 patients took CCRT ( 60 Gy, 30 #, weekly
cisplatin 30 mg/m2)
 Among those non resected patients 167 were treated with CCRT ( 70 Gy, weekly
cisplatin), 3 patients were given definitive RT alone , and the rest were put on
palliative treatment.

61. Cont’d
After a median follow up of 28 months
 The estimated median survival for those patients who didn’t receive
adjuvant Rx after surgery is 16.6 months but, it is unreached in those
patients who were treated with surgery plus adjuvant therapy
Patil MV et al.
after NACT
Surgically Rxed Non surgical
Rx
Whole
cohort
P value
Median OS 19.6 months 8.6 months 10.8 months 0.0001
2 year OS 47 % 20 %
2 year LRC 32 % 15 % 0.0001

64. Unresectable Disease
 Chemotherapy combined with radiotherapy is the preferred treatment for
patients with unresectable locally advanced squamous cell carcinoma of the oral
cavity.
 Tumors with one or more of the following characteristics
- encasement of the carotid artery
- skull base invasion
- involvement of the pre-vertebral fascia
 A number of randomized trials and several meta-analyses have demonstrated
improved outcomes with concurrent chemotherapy as compared to sequential
treatment or radiation therapy alone for patients with locally advanced head-
and-neck cancers.
 Extrapolating this trend for managing cases with OC-SCC…………??? ( low
number of cases of OCSCC were represented in this patient population)

65. Organ/function preserving treatment
 No prospective studies have been conducted specifically investigating surgery
versus chemoradiation for oral cavity cancer
 Over the past two decades some institutions has adopted a paradigm of upfront
organ function preservation using definitive CCRT for locally-advanced OC-SCC with
surgery reserved for salvage as necessary
 Analysis of 20-year (1994 to 2014) experience of upfront CCRT for locally-advanced
OC-SCC from Chicago university was reported
 Taxane and platinum-based induction chemotherapy was delivered prior to CRT on
several patients and lasted for a period of 6–8 weeks followed by FHX based CCRT
- Chemotherapy = 5 FU and hydroxyurea with other third agents.
- RT once or twice daily to a maximum dose of 70–75 Gy.
- IMRT was exclusively used after 2004

66. Cont’d
 During the first decade of treatment, post-CRT neck dissection was
routinely performed for patients with N2- N3 neck disease;
 In the second decade, post-CRT neck dissection was generally triggered by
any radiologicaly or clinically detected large or focally-abnormal lymph
node
 Tumor outcomes were compared across treatment decades using the log-
rank test ( 1994 – 2003 Vs 2004 – 2014)

68. Cont’d
 Patients were followed for a median of 5.7 years
 There was a trend to wards improved OS in the 2nd decade ( P = 0.1)
 There was no significant difference in the LRC,PFS, and DC b/n decades of
treatment
 ORN = 20 % and the most important risk factor was primary tumor of the FOM
 Induction chemotherapy was not associated with LRC, DC, PFS or OS
 Definitive CRT is a viable and feasible strategy for organ preservation for patients
with locally advanced OC-SCC.
N = 140 1st decade
( n = 64)
2004 – 2014
( IMRT) n = 76
Whole
cohort
T3/T4
disease
p value
for 1st & 2nd decades
5 yr OS 58.2 % 67.6 % 63.2 % 57.8 % 0.1
5 yr PFS 56.7 % 60.6 % 58.7 % 52.8 % 0.38
5yr LRC 77.3 % 79.8 % 76.8 % 72.8 % 0.9
5 yr DC 84 .3 % 89 .9 % 87.2 % 85 % 0.25

70. Cont’d
 Several retrospective studies have also investigated the efficacy and toxicity of organ
preservation for OC-SCC
 The MSKCC reported their results for 73 patients with OC-SCC treated with definitive CRT
from 1990 to 2011.
 With median follow-up of 73.1 months, 5-year OS was 15% and 5-year LRC was 37%.
 Moreover, a recent National Cancer Database (NCDB) analysis reported 3-year OS of 37.8%
for 2091 patients receiving definitive CRT for OC-SCC
 This discrepancy in oncologic outcomes among reports likely results from
- patient selection for definitive CRT which is usually limited to those with
high comorbidity or advanced disease
 In fact, patients receiving definitive CRT in the NCDB analysis were found to be statistically
significantly more likely to be
older than 60,
treated at nonacademic centers,
have more comorbidities, and
have clinical T3/T4a as well as N2a-N2c diseases

72. Follow-up/ surveillance

73. Cont’d
 Nutritional evaluation and rehabilitation as clinically indicated until
nutritional status is stabilized
 Smoking cessation and alcohol counseling
 In patients with cancer of the oral cavity, the risk of developing a second
primary cancer is well recognized.
 Second primary cancers have an adverse effect on prognosis and are the
major cause of treatment failure in patients with early-stage disease.
 The probability of developing a second metachronous malignancy at 5
years was 22% (18% for the subset of patients with oral cavity cancer)

74. Cont’d
 Quitting tobacco and alcohol use greatly reduces the risk of developing
subsequent head and neck squamous cell carcinoma.
 Individuals that have stopped smoking for 1 to 4 years have a 30%
decrease in risk of developing carcinoma of the head and neck compared
to those that continue to smoke.
 For those that quit smoking beyond 20 years, the risk parallels that of
never smokers; a similar effect is seen with stopping the use of alcohol
 Therefore, continued efforts toward tobacco and alcohol cessation are a
central strategy in the management of patients with oral squamous cell
carcinoma

75. Case critics
• Inadequate documentation
• Patient didn’t receive concurrent
chemotherapy
• The treatment beams on the opposed lateral
fields were not weighted.

76. References
1. Perez and Brady's Principles and Practice of Radiation Oncology, 7th Edition,
2. DeVita , Hellman, and Rosenberg’s Cancer Principles and Practice of Oncology, 11th
edition
3. Gunderson and Tepper clinical radition oncology 4th edition
4. Clinical radiation oncology, indications, techniques and results, 3rd edition
5. Upto date 2018
6. NCCN Guideline anal ca version 1.201
7. Scher ED, Romesser PB, Chen C, Ho F, Wuu Y, Sherman EJ, et al. Definitive
chemoradiation for primary oral cavity carcinoma: a single institution experience. Oral
Oncol 2015;51(7):709–15.
8. Spiotto MT, Jefferson G, Wenig B, Markiewicz M, Weichselbaum RR, Koshy M.
Differences in survival with surgery and postoperative radiotherapy compared with
definitive chemoradiotherapy for oral cavity cancer: a National Cancer Database
analysis. JAMA Otolaryngol Head Neck Surg 2017;143(7):691–9.
9. Google search