Clinical Presentation and Work-Up of SCC of the Oral Tongue

  • Clinical presentation of oral tongue cancer:
    • Patients with oral cancer may present with several symptoms notably:
    • Pain
    • Ulceration
    • A lump on the tongue
  • Lesions of the oral tongue:
    • Are more likely to be symptomatic than lesions of the base of the tongue:
      • Although despite this many patients still present with a four- to six-month history of symptoms prior to seeking medical advice
    • The majority of patients with cancer of the oral tongue present with stage I / II disease:
      • Which contrasts significantly with cancers of the base of the tongue that are usually stage III / IV at presentation
    • Clinically positive cervical lymphadenopathy at presentation:
      • Is in the region of 21% to 34%:
        • Occult cervical metastasis has been demonstrated in up to 53% of patients with tongue cancer:
          • Being related to tumor thickness
        • Tumors arising on the lateral aspect of the tongue tend to be thicker than those of the ventral aspect of the tongue:
          • Up to 4.5% may have occult cervical disease in the contralateral neck
        • Clinical examination, CT and MRI:
          • Have relatively poor sensitivity at determining cervical lymph-adenopathy
  • The majority of tongue tumors:
    • Are well to moderately differentiated on histological examination
  • Work up:
    • As with many sites, management of the neck is frequently determined by tumor thickness:
      • Tumor thickness can be assessed accurately with intraoral sonography, or immediate sonography of the resected tumor:
        • Prior to proceeding to a neck dissection if access to the neck is not required for reconstructive purposes
    • Biopsies should endeavour to include the deep margin of the tumor in addition to mucosa at the periphery of the tumor:
      • Deep biopsies may give an indication of tumor depth:
        • But also multifactorial histological malignancy grading of the most dysplastic areas of the invasive front may help in assessing the risk of cervical metastasis
#Arrangoiz #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncology #TongueCancer #MountSiniaMedicalCenter #MSMC #Miami #Mexico

CALBG 9343 Trial

  • The CALGB 9343 study:
    • Enrolled 647 patients:
      • From 1994 until 1999
    • Long-term follow-up data were published in 2013:
      • With a median follow-up of 12.6 years
    • Women age 70 years or older with clinical stage I (T1N0M0) ER+ breast cancer treated by lumpectomy:
      • Were randomly assigned to receive tamoxifen plus radiation therapy (TamRT) or Tam alone
    • At 10 years:
      • 98% of women receiving TamRT were free from local and regional recurrences:
        • Compared to 91% of those receiving Tam
    • The 10-year estimates of overall survival (OS) were:
      • 67% (95% confidence interval [CI], 62–72%) in the TamRT group versus 66% (95% CI, 61%–71%) in the Tam group:
        • But the difference was not statistically significant
  • In addition to concluding that while RT (in addition to Tam) reduces locoregional recurrence:
    • The authors noted that “the impact of breast cancer in this select group of older women is much smaller than that of comorbid conditions:
      • Only 3% of women in study have died as a result of breast cancer:
        • Whereas 49% have died as a result of other causes
  • References:
    • Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol.2013;31(19):2382-2389.
    • Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31:2382-2389.
#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #BreastCancer #OmittingRadiation #MountSinaiMedicalCenter #MSMC #Miami #Mexico

Recurrence Rate for Oral Tongue Carcinoma

  • Recurrence rates for oral tongue carcinoma are:
  • 10% to 50%:
    • Usually being locoregional
  • Similar to other sites:
    • Recurrence usually occurs within the first two years
  • Factors that influence local recurrence include:
    • Tumor thickness
    • The presence of perineural spread
  • It has been proposed that recurrence of thicker tumors:
    • Is related to difficulty in assessing deep clearance intraoperatively compared to assessing mucosal clearance
  • Patients younger than 40 years:
    • Have been demonstrated to be significantly more likely to develop locoregional failure:
      • Although this does not influence survival
  • 10% of patients who have developed a tongue tumor:
    • Will develop metachronous second tumors of the oral cavity
#Arrangoiz #CancerSurgeon #SurgicalOncologist #HeadandNeckSurgeon #HeadandNeckCancer #MountSinaiMedicalCenter #MSMC #Miami #Mexico

NSABP B-40 Trial

  • Recognizing that bevacizumab, capecitabine, and gemcitabine:
    • Have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer:
      • The NSABP B-40 trial:
        • Was designed to determine whether adding capecitabine or gemcitabine to docetaxel, followed by anthracycline doxorubicin and cyclophosphamide (AC):
          • Would improve the outcomes in patients with operable, HER2-negative breast cancer
      • The trial also sought to determine the effect of adding bevacizumab to these neoadjuvant chemotherapy regimens
      • Patients were divided into three groups:
        • Docetaxel followed by AC
        • Docetaxel and capecitabine followed by AC
        • Docetaxel plus gemcitabine followed by AC
        • Each of these three groups was then randomized to receive:
          • Bevacizumab with the first 6 cycles of chemotherapy or not, for a total of 6 treatment arm
        • The addition of capecitabine or gemcitabine to docetaxel therapy, compared to docetaxel alone:
          • Did not significantly increase the rate of pCR:
            • 29.7% and 31.8%, respectively, vs 32.7%; P=0.69
          • Both capecitabine and gemcitabine were associated with:
            • Increased toxic side effects such as hand-foot syndrome, mucositis, and neutropenia
        • However, the addition of bevacizumab significantly increased the rate of pCR in the breast:
          • From 28.2% to 34.5% (P=0.02):
            • This effect was more pronounced in the hormone receptor-positive subset of patients:
              • 15.1% pCR without bevacizumab vs 23.2% with bevacizumab:
                • However, the addition of bevacizumab also increased rates of hypertension, left ventricular systolic dysfunction, hand-foot syndrome, and mucositis
  • References:
    • Bear HD, Tang G, Rastogi P, Geyer Jr CE, Robidoux A, Atkins JN, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366(4):310-320.
    • NSABP clinical trials overview. Protocol B-40. A randomized phase III trial of neoadjuvant therapy in patients with palpable and operable breast cancer evaluating the effect on pathologic complete response (pCR) of adding capecitabine or gemcitabine to docetaxel when administered before AC with or without bevacizumab and correlative science studies attempting to identify predictors of high likelihood for pCR with each of the regimens. National Surgical Adjuvant Breast and Bowel Project website. http://www.nsabp.pitt.edu/B-40.asp. Accessed May 15, 2020
#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #MountSinaiMedicalCenter #MSMC #Miami #Mexico

Postoperative Radiotherapy (PORT) for SCC of the Tongue

  • PORT has been advocated for:
    • Positive margins
    • Multiple cervical nodes
    • Extracapsular spread in the neck
    • Stage III / IV disease
    • Perineural spread
    • Tumors thicker than 9 mm to 10 mm even in the absence of other features
  • Based on involved margins, ECS of cervical nodes or multiple positive nodes:
    • 62% of patients receiving surgery as the primary treatment modality may require PORT
  • Local failure following PORT to tongue tumors has been demonstrated to be higher than comparable floor of mouth tumors:
    • Leading some to suggest higher doses of PORT should be considered for tongue tumors
#Arrangoiz #CancerSurgeon #SurgicalOncologist #HeadandNeckSurgeon #SCC #MountSinaiMedicalCenter #MSMC #Miami #Mexico

Epidemiology of SCC of the Oral Tongue

  • In populations where tobacco chewing is not endemic:
    • The oral tongue is one of the most common sites for oral cancer:
      • 22% to 39% of oral cancers developing at this site
  • Within the site:
    • Most tumors occur in the middle third of the tongue:
      • Commonly on the lateral aspect:
        • Followed by the ventral aspect of the tongue
    • Only 4% to 5 % of tongue carcinomas occur on the dorsum of the tongue
  • Tongue cancer:
    • Occurs slightly more frequently in males:
      • The age at diagnosis usually being in the sixth to eighth decades:
        • 90% of patients being greater than 40 years of age
      • The male-to-female ratio has decreased in recent years:
        • Possibly due to increased alcohol consumption by females
  • Smoking and alcohol consumption:
    • Is common among patients with tongue cancer:
      • Up to 70% describing significant tobacco and alcohol use
#Arrangoiz #CancerSurgeon #Miami #MountSinaiMedicalCenter #MSMC #Mexico #HeadandNeckSurgeon #TongueCancer

Management of the Neck for Tongue Cancer

  • Tumors of the tongue:
    • Initially metastasize to levels I and II:
      • Lateral tongue tumors frequently metastasizing directly to level II nodes
    • Involvement of level V nodes:
      • In the absence of positive nodes in levels I to IV is rare:
        • However it is not unusual for nodes in level IV to be involved:
          • Hence even in elective neck dissections levels I to IV should be dissected
  • Like floor of mouth tumors:
    • The presence of lingual lymph nodes should be considered and either an in-continuity resection with the neck specimen or clearance of tissue above the mylohyoid conducted
  • Bilateral neck dissections:
    • Should be considered in tumours that extend to or beyond the midline.
  • The management of the neck in larger primary tumors:
    • Is usually straightforward since the neck is accessed for microvascular or pedicled flap reconstruction of the primary site
    • Management difficulties arise with smaller tumors amenable to peroral resection and local closure
  • It has been proposed that the increased incidence of nodal metastasis associated with tongue carcinoma:
    • May be due to contraction of tongue muscles promoting entry of cancer cells into the lymphatics
    • It is thought that mechanism by which tumor thickness is related to cervical metastasis:
      • Is that thicker tumors have access to wider lymphatics:
        • In which tumor emboli can form more readily
    • Although tumors arising on the lateral aspect of the tongue tend to be thicker than those of the ventral aspect of the tongue:
      • This may not manifest as a greater risk of cervical metastasis, since the ‘critical thickness’ for tumors of the floor of mouth is less than other oral sites
  • Elective neck dissection or elective neck radiotherapy:
    • Should be considered for tumors thicker than 3 mm to 4 mm:
      • T2 or greater in dimension and T1 tumors that demonstrate poor histological features:
        • Poor differentiation
        • Double DNA aneuploidy
        • Degree of differentiation at the advancing front
  • Elective neck dissection:
    • Significantly improves loco-regional control:
      • It has been demonstrated that conducting an END reduces regional recurrence from 47% in ‘watch and wait’ patients to 9% if END is conducted
  • END has been shown by some to improve five-year survival:
    • The five-year survival of patients undergoing therapeutic neck dissection following a ‘watch and wait’ policy being 35% as opposed to 69% when an elective neck dissection is conducted
      • Others, however, have not demonstrated a survival advantage
#Arrangoiz #CancerSurgeon #MountSianiMedicalCenter #MSMC #Miami #Mexico

Surgical Anatomy of the Oral Tongue

  • The oral tongue:
    • Is the freely mobile anterior two-thirds of the tongue
  • The oral tongue is demarcated from the base of tongue by:
    • The circumvallate papillae posteriorly
  • The tongue may be subdivided into:
    • The tip, dorsum, lateral borders and ventral surface
  • The ventral and lateral surfaces:
    • Are in continuity with the floor of mouth:
      • Having a lining mucosa with nonkeratinizing stratified squamous epithelium
  • The dorsum and tip of tongue:
    • Are lined by specialized gustatory mucosa:
      • With a thick, primarily keratinized epithelium
  • The mucosa of the tongue:
    • Overlies the intrinsic muscles of the tongue, in addition to the four paired extrinsic muscles of the tongue:
      • Genioglossus
      • Hyoglossus
      • Styloglossus
      • Palatoglossus
  • Motor innervation to muscles of the tongue:
    • Is via the hypoglossal nerve, except palatoglossus:
      • Which is supplied by the vagus nerve
  • Sensation of the tongue is supplied by the lingual nerve:
    • A branch of the mandibular division of the trigeminal nerve
  • Taste sensation of the oral tongue:
    • Is supplied by fibers of the facial nerve that run with the lingual nerve before passing to the chorda tympanic branch of the facial nerve
  • Lymphatic drainage of the lateral borders of the tongue:
    • Is to the ipsilateral cervical nodes
  • Drainage of the midline, tip and base of tongue:
    • Occurs bilaterally
  • The blood supply to the tongue:
    • Is provided by the paired lingual arteries:
      • The third branches of the external carotid artery
  • During resection of posterior tongue lesions:
    • The contralateral vascular pedicle should be preserved if the tongue tip is to be maintained
  • The tongue is a complex structure with an important role in:
  • Mastication, deglutition and speech
#Arrangoiz #CancerSurgeon #MountSinaiMedicalCenter

Treatment of the Primary Site of a Squamous Cell Carcinoma of the Tongue

  • Resection of the tumor:
    • With a 1 cm margin in three dimensions:
      • Should be conducted if surgery is the treatment of choice
  • The use of ultrasonography :
    • To aid in assessment of surgical clearance had been advocated by some:
      • Particularly for the deep margin
  • Frozen section:
    • Can be used (its my practice) but some centers do not routinely used it:
      • Even with apparently adequate margins during surgery:
        • 10% of resections may demonstrate histologically positive margins
  • The aim of reconstruction of the oral tongue following resection:
    • Is to ensure maximum function of the residual tongue tissue:
      • Since the complex function of the tongue cannot be replicated with current reconstructive techniques
    • Preservation of the tip of the tongue:
      • While maintaining oncologically sound resection margins:
        • Helps maximize postoperative function
  • The use of monopolar electrocautery:
    • Cutting through mucosa changing to coagulation when in muscle, or the harmonic scalpel:
      • Helps reduce bleeding during the resection:
        • However this is at the cost of lack of feel afforded by the use of scalpel or scissors
  • If both lingual vessels are resected:
    • Then the viability of the tip of tongue remnant should be carefully assessed:
      • Sacrifice of both hypoglossal nerves results in a nonfunctioning tongue tip
  • Small lesions may be removed with a laser and allowed to heal by secondary intention
  • T1 and small T2 primary tumors:
    • May be excised with a vertical wedge and the defect closed primarily:
      • If the defect does not extend to significantly to include the floor of mouth
    • Many larger lesions benefit from free flap reconstruction of the defect:
      • Usually with a radial free forearm flap:
        • Although the anterolateral thigh free flap is being used more frequently
      • The skin paddle of the chosen free flap:
        • Should be fashioned so as not to restrict residual tongue function and should hopefully augment swallowing
      • Typically, the reconstruction should be of the same size, or slightly smaller than the defect created by the resection
      • Care should be taken in the design of the flap:
        • When the defect extends to include adjacent sites:
          • Such as the soft palate or floor of mouth
      • The mobile tongue and floor of mouth:
        • Should be ‘separated’ in the reconstruction:
          • To minimize restriction of movement of the residual tongue
      • Thin radial free flaps may have their bulk increased by extending fascial flaps beyond the skin island:
        • The fascial flaps then being folded and buried underneath the epithelial reconstruction
    • Reconstruction of large resections:
      • May be accompanied by measures aimed to improve postoperative function:
        • Such as static laryngeal suspension to the mandible and cricopharyngeal myotomy
    • Once the specimen is removed, it is examined for clearance and orientated for the pathologist:
      • A digital photograph being useful
  • Radiotherapy as the primary treatment modality can be used in certain situations:
    • Has been advocated since it conserves tongue volume and morphology:
      • Brachytherapy being considered preferable to external beam radiotherapy:
        • Osteoradionecrosis of the mandible is a recognized complication of brachytherapy of the tongue:
          • Up to 9% developing some form of osseous complication
        • The use of brachytherapy to the primary site:
          • Requires either surgery or external beam radiotherapy to the neck in an elective or therapeutic manner:
          • When surgery is not conducted as the primary treatment:
            • Valuable prognostic information is lost:
              • Since the primary tumor is not examined histologically:
                • This makes the decision as to whether to conduct an END more difficult
          • It has been suggested that surgery is superior to brachytherapy in the management of stage I / II tongue cancer:
            • By conducting surgery as the primary treatment modality, radiotherapy is kept in reserve for either poor prognostic indicators of the resected specimen, for management of recurrence or management of second primaries which commonly occur at a later date
#Arrangoiz #HeadandNeckSurgeon #CancerSurgeon #MountSinaiMedicalCenter #MSMC #SurgicalOncologist

Treatment of Floor of the Mouth Squamous Cell Carcinomas

  • Primary Site:
    • The need for aggressive treatment of floor of mouth carcinomas:
      • Is well recognized
    • Surgical resection with a 1 cm margin should be achieved:
      • If surgery is the preferred treatment modality
    • Even in the best surgeon’s hands:
      • Positive or close margins may be seen in up to 47% of resections:
        • Despite the use of intra-operative frozen section:
          • Many floor of mouth tumors are infiltrative with indistinct edges:
            • Possibly explaining the high incidence of positive margins
        • Further resection is advocated if margins are positive
      • Although 1 cm margins are considered by most surgeons to be adequate:
        • Extended 2 cm margins have been advocated by some
    • The early extension of floor of mouth tumors into the tongue or mandible:
      • Is demonstrated by the fact that many patients require marginal (rim) or segmental resection of the mandible
    • Surgical resection of the floor of mouth in the majority of circumstances:
      • Will involve resection of part of the submandibular ducts:
        • Typically, the ducts will be resected at the resection margin, well away from their orifice:
          • However in smaller resections at least 3 mm length of duct proximal to the orifice:
            • Should be taken to ensure surgical clearance of carcinoma or dysplasia that may extend along the duct
          • Management of the submandibular ducts is of great importance if a neck dissection is not being conducted with consequent removal of the submandibular gland:
            • Stricture of the duct in the presence of a functioning gland:
              • May give rise to obstructive symptoms of the gland and difficulty in differentiating the potential submandibular gland swelling from cervical disease
        • The ducts should be transected obliquely to minimize stricture formation and repositioned at the margin of resection, ideally being stented
        • Alternatively, the ducts may be found proximal to the resection margin:
          • A longitudinal incision made and the duct marsupialized’ to the floor of mouth mucosa:
            • Uninvolved branches of the lingual nerve should be identified and preserved
    • Small resections:
      • May be left to heal by secondary intention or a split thickness skin graft applied
    • A more substantial reconstruction may be achieved using local nasolabial or facial artery musculomucosal flaps:
      • However an edentulous segment is required when using both of these flaps to accommodate their pedicle
    • If a neck dissection is required and surgical facilities allow;
      • Microvascular reconstruction provides a far more flexible reconstructive option, without necessarily prolonging operative time if a two team approach is adopted
Reconstruction with split skin graft
  • The radial free forearm flap is an ideal reconstructive option for floor of mouth defects:
    • Easily being converted to a composite flap if segmental resection of an edentulous mandible is required
  • Prefabricated fasciomucosal free flaps have been described in oral reconstruction:
    • However their role in oncological reconstruction is questioned
  • The fibula osteocutaneous flap provides superior reconstruction if a segmental resection is anticipated in a dentate patient:
    • Although like the composite radial free flap:
      • Flexibility of the skin paddle is limited
  • The scapula osteocutaneous flap:
    • With two skin paddles, or one skin paddle and muscle left to mucosalize:
      • Provides an excellent reconstruction of large defects involving mucosa, bone and external skin
  • Radiotherapy techniques (brachytherapy or external beam):
    • For T1 / T2 primaries have been shown to provide results similar to surgery
    • The proximity of the floor of the mouth to the mandible:
      • Is of concern when using brachytherapy:
        • Since up to 8.5% of patients treated with this modality require segmental resection of the mandible:
          • Due to osteoradionecrosis within 10 years
    • Several units have described a change in practice from brachytherapy to surgery:
      • As the primary treatment modality due to the risk of complications
    • T3 / T4 lesions:
      • Are best treated with surgery and postoperative radiotherapy
  • Management of the Neck in Floor of the Mouth SCC:
    • Regional spread of disease in floor of mouth carcinomas is usually to the ipsilateral level I to III lymph nodes:
      • Involvement of multiple levels not being unusual
    • Lesions towards the midline:
      • May spread to both sides of the neck:
        • Hence bilateral neck dissections should be considered
    • The presence of lingual lymph nodes:
      • Has raised the concept of in-continuity neck dissection in an attempt to reduce local recurrence and improve survival:
        • Resection of the tumor accompanied with the complete clearance of the floor of the mouth, preserving mylohyoid, hyoglossus and genioglossus if possible, so clearing the lingual lymph nodes would seem an acceptable method of managing lingual lymph nodes
    • The decision to conduct an elective neck dissection has been related to tumor size or depth of invasion:
      • Lesions that are T2 or greater:
        • Should have an elective I to III / IV selective neck dissection:
          • Although elective neck dissections have been advocated for T1 lesions
    • Tumor thickness of 4 mm is often used as a ‘generic’ critical thickness, greater than which an elective neck dissection is indicated:
      • Since the risk of occult metastasis is greater than 20%:
        • It has been demonstrated that the risk of cervical metastasis of floor of mouth tumors exceeds 20% in tumors as thin as 1.5 mm to 2 mm:
          • Using a thickness of 1.5 mm may result in up to 32% of patients requiring END based on thickness criteria
  • The indications for postoperative radiotherapy to the loco-regional area are similar to other sites:
    • Notably two or more involved nodes in the neck
    • Extracapsular spread
    • Positive margins
    • Stage III / IV disease
  • Postoperative radiation therapy (PORT):
    • The beneficial role of PORT in selected patients with floor of mouth carcinoma has been demonstrated
  • Recurrence:
    • Recurrence rates for floor of mouth carcinoma are 26% to 55%:
      • Usually within the first two years
    • Factors that influence recurrence include:
      • Tumor size
      • Margin status
      • Tumor thickness
      • Advanced nodal disease
  • Prognosis
    • Overall five-year survival for floor of mouth carcinoma:
      • Is 52% to 76%
    • Factors that potentially influence survival include:
      • Nodal status
      • Thickness
      • Margin status
      • Recurrence
#Arrangoiz #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncologist #Miami #Mexico #MountSianiMedicalCenter #MSMC