OBSERVATIONS ON CANCER TREATMENT AND REHABILITATION
From Update in Head and Neck Cancer: 2008, presented by the Massachusetts Eye and Ear Infirmary,
Massachusetts General Hospital, and Harvard Medical School
Educational Objectives
| The goal of this program is to improve the management of laryngeal cancer. After hearing and assimilating this
program, the clinician will be better able to:
|
 | 1. Describe the organ-preserving options available to a patient facing possible total laryngectomy.
|
| 2. Determine when total laryngectomy is indicated.
|
| 3. Discuss the latest advances in treatment precision with radiation therapy.
|
| 4. Review the outcomes of radiation therapy in early and advanced glottic cancer.
|
| 5. Utilize methods for improving postchemoradiation dysphagia.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee
to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the following has been disclosed: Dr. Harari has a laboratory research agreement
with Agmen, AstraZeneca, Genentech, and Imclone Systems Inc. Dr. Bradford, Ms. Goldsmith, and the planning committee
reported nothing to disclose.
Acknowledgements
Drs. Bradford and Harari and Ms. Goldsmith were recorded at Update in Head and Neck Cancer: 2008, held April
18-20, 2008, in Boston, MA, and sponsored by the Massachusetts Eye and Ear Infirmary, Massachusetts General
Hospital, and Harvard Medical School. The Audio-Digest Foundation thanks the speakers and the sponsors for their
cooperation in the production of this program.
| LARYNGECTOMY IN THE CHEMORADIATION ERA —Carol R. Bradford, MD, Professor and Associate Chair of
Clinical Programs and Education, Department of Otolaryngology–Head and Neck Surgery, and Co-Director, Head and
Neck Oncology Program, University of Michigan Medical School, Ann Arbor
|
| Options for advanced larynx cancer: organ-preserving surgery—supracricoid laryngectomy, including preserving
epiglottis or not and affixing hyoid to cricoid cartilage; for effective surgery, tumor must be free of cricoid cartilage;
other forms of open and laser subtotal laryngectomy; transoral laser microsurgery gaining popularity; many options make
decision difficult and complicated; survival not improved by chemotherapy and radiation, relative to surgery and radiation;
organ preservation main argument for use of chemotherapy and radiation; if effective and functional organ-preservation
strategies available using primary surgery, choose those strategies; other options include radiation with salvage
surgery, sequential chemoradiation, concurrent chemoradiation, and induction chemotherapy followed by radiation or
chemoradiation; use evidence-based randomized controlled clinical trials to make decision
|
| Role of primary surgery: total laryngectomy—one of surgical procedures most feared by patients; social isolation,
job loss, and depression common sequelae; stoma biggest dilemma (inability to swim under water); best way to achieve
local-regional control for advanced larynx cancer; in study of patients who survived cancer treatment, pain, speech, and
depression better in chemotherapy and radiation arm; scores better on chemoradiation domain for mental health and pain,
with less posttreatment depression in those whose larynx preserved, compared to those whose larynx removed; survival
primary end point of successful treatment; primary laryngectomy—controversial whether it should be considered for all
T4 tumors; two University of Michigan Cancer Center (UMCC) 9520 clinical trials published in Journal of Clinical Oncology
involved single cycle of induction chemotherapy; responders with >50% response at primary site went on to concomitant
radiation therapy, followed by adjuvant therapy if they remained clinical and histologic complete response;
patients with <50% response at primary site had early salvage surgery (conservative or total laryngectomy) followed by
radiation therapy; trial—same strategy, except that patients who achieve complete response at primary site could go on
to chemotherapy alone (5 cycles of chemotherapy); stopped early due to local-regional relapse; no longer doing primary
chemotherapy alone for head and neck cancer
|
| Study: looked at quality-of-life measurements related to understandability of speech; 38 patients met criteria, 20 of whom
had extralaryngeal spread and 18 of whom had cartilage invasion alone; median age 58 yr (75% men, 25% women); two-
thirds supraglottic, one-third glottic, and few hypopharynx; most N0 or N2, with only one N3 patient; 30 patients had
>50% response at primary site and went on to chemoradiation (per protocol); 7 patients had <50% response, with 6 eventually
receiving salvage laryngectomy (per protocol); 26 of 30 achieved histologic complete response, of whom 3 suffered
late failure; 4 of 30 patients had persistent disease after chemoradiation and had laryngectomy; of 38 patients, 23
alive, with 21 cancer-free (16 in chemoradiation group; 7 had laryngectomy); of those who did not survive, 9 had chemoradiation
and 6 had laryngectomy; 3-yr local–regional control 76%; 3-yr disease-free survival 64%; 3-yr laryngectomy-
free survival (actuarial) 71%; overall survival 76% at 3 yr, with median follow-up of 48 mo; compared results with larger
cohort of patients with T3 primary tumors; follow-up slightly shorter in T4 patients; better results seen in T3 patients,
with exception of laryngectomy-free survival (not statistically different); in general, T3 tumors had better survival than
T4 tumors; with time to laryngectomy or indication for laryngectomy, results not dramatically different; 6 of 38 patients
had early laryngectomy (easier from surgical standpoint because tissues not heavily pretreated, heal well, free flap not
necessary, and less concern for hospitalization and fistula formation); 4 had late laryngectomy (after chemotherapy and
radiation); 3 had delayed laryngectomy for recurrent disease; 63% of patients had intact larynx, 72% had cartilage invasion
alone, and 55% had extralaryngeal spread; understandability of speech 75% to 100% in majority of both groups; important
to consider functional nature of laryngeal preservation, particularly in T4 group; among T4 patients, 16%
gastrostomy (G)-tube dependent (4% in T3 patients); tracheostomy tube present in 16% with larynx preservation and
12% of T3 patients (not statistically different); overall survival at 3 yr 76% for T4 patients (84% for T3 patients); consider
performing total laryngectomy up front for patient with tumor that involves cartilage and support of larynx and
those with high G-tube dependence rates, with tumor extending through thyroid cartilage into soft tissues of larynx; most
important outcome always survival
|
| Integration of surgery into clinical trials for cancer of larynx: cause-specific survival for UMCC 9520 study
≈89% at 2-yr interval and 87% at 3-yr interval; with early response to induction chemotherapy, able to perform early laryngectomy
and as such, no difference seen in overall survival probability in organ-preservation group or in laryngectomy
group; always dilemma in heavily pretreated patient to identify recurrent cancers early on when salvage still
possible
|
| Success of salvage surgery after chemoradiation: in heavily pretreated chemoradiated patient, options include
conservation laryngeal surgery or total laryngectomy; structure of larynx allows for salvage of chemoradiation failures,
although number of treatments adds morbidity and potential for complications; pharyngeal-covering graft used to prevent
major wound complications; using free flap to cover closure or pectoralis major flap does not prevent minor complications,
but makes wound infections more self-limited (managed in outpatient setting); take-home points—personalized
approach; utilize biomarkers; try to limit heaviness of treatment; each treatment adds morbidity; goal to cure cancer with
least morbidity; salvage surgery challenging and risky; patients may fare better with earlier surgery; team effort critical to
successful care
|
| RADIATION THERAPY FOR LARYNGEAL CANCER —Paul M. Harari, MD, Jack Fowler Professor and Chair, Department
of Human Oncology, University of Wisconsin School of Medicine and Public Health, and Associate Director,
Paul P. Carbone Comprehensive Cancer Center, Madison, WI
|
| Treatment precision: previously, crayons used on patient to demarcate beam, with “x” marks to demarcate isocenter of
beam and junction of lateral beam with anterior beam; day-to-day reproducibility challenging; physical targeting—
enhanced technical precision of surgery and radiation; improved reconstruction and rehabilitation through diminished
collateral damage of treatment; large lateral beam shrunk to area of risk and big anterior beam to finish treatment of low
anterior neck nodes; previously, most common radiation technique for most advanced larynx cancer (still commonly
used); new technologies—intensity-modulated radiation therapy (IMRT) one of most commonly used; tomotherapy another
form of IMRT; proton therapy enables full dose to primary tumor with more sparing of normal tissue
|
| Larynx cancer: goals—achieve cure; preserve speech; optimal swallowing capacity; stages—include early, moderately
advanced, and very advanced; relates to T stage and indirectly to N stage; in early stage, high chance of cure with
voice preservation; in moderately advanced stage, relatively high chance of voice preservation; in very advanced stage,
moderate chance of cure, with small chance of laryngeal voice preservation; complementary to TNM staging; early glottic
cancer—3 primary treatment approaches include transoral laser surgery, radiation, or open partial laryngectomy; radiation
therapy— be careful about delineation of beam for early glottic cancer; not too many photon beams smaller than
4x4 cm or 5x5 cm, unless performing stereotactic ablations; larynx can move out of beam during swallowing; dosimetry
challenging with field sizes <4 cm; 2 common fractionation approaches in United States to deliver 66 gray (Gy) in 2 Gy
fractions over 6.5 wk for T1 or early T2 lesion; for more robust T2 lesion, up to 70 Gy; another regimen commonly used
to increase fraction size slightly, achieving 63 Gy
|
| Outcomes for early glottic cancer with radiation therapy: best data from University of Florida; series of 519
patients over 3 decades; local control rates for T1 with primary irradiation 93% to 94%, with drop in local control for T2
and particularly T2b; reason for high local control rates that glottis one of head and neck sites effectively salvaged with
surgery; neck control not major issue if staging accurate and patient truly T1 or T2; cause-specific survival low in early
glottic cancer, but at 5 yr, death due to comorbid and other second malignancies; advanced glottic cancer—consider
going beyond T staging (low-volume vs high-volume lesions different entities in treatment approach); low-volume favorable
cases have option for chemoradiation; argued that for low-volume lesions, radiation alone adequate or open partial
laryngectomy; high-volume unfavorable lesions best served with total laryngectomy and neck dissection
|
| Supraglottic cancer: also consider volume; for low-volume lesions, radiation or partial laryngectomy good options; for
high-volume lesions, more likely total laryngectomy involved; in N0 lesions, often see pulling down away from salivary
glands to some degree, so that even with conventional techniques, still have effective treatment of larynx cancer; 5-yr local
control rates using radiation alone good; in maintenance of local control and functional larynx, smaller volume tumors do
well; with large-volume tumors, must be cautious about pushing for irradiation as ideal for local control and functional larynx
(from radiation-alone data, which does not incorporate concurrent chemoradiation approaches); meta-analysis showed
that chemotherapy had impact when added to radiation; concurrent chemoradiation treatment approach 2008 standard of
care for many advanced head and neck cancers, including larynx; local-regional control and larynx preservation best with radiation
and concurrent platinum-based chemotherapy; how platinum given still issue; speaker believes nonprotocol weekly
use better (although clinical trial data not as robust); question of whether postradiotherapy or chemoradiotherapy neck dissection
should be mandated for N2 lesion or whether this should be image-based; other questions include role of altered
fractionation and schedule of platinum or total exposure of platinum; cetuximab—emerging alternative option; when added
to radiation, survival benefit seen, although on subset analysis, no discernible advantage for larynx cancer (dominant advantage
seen in oropharynx cancer); IMRT practitioner-dependent; warn patients about dangers of smoking and alcohol use
|
| Age: small benefit for altered fractionation disappears when patient ≥70 yr of age (also with chemotherapy); consider
whether age should play role when selecting therapies
|
| Long-term follow-up: from radiation standpoint, significant toxicities seen in long-term follow-up; speaker believes
that sometimes valuable for nonsurgeon to advocate total laryngectomy; patient’s prerogative to choose from options presented
|
| REHABILITATION OF POSTCHEMORADIATION DYSPHAGIA —Tessa Goldsmith, MA, CCC-SLP, Assistant Director,
Department of Speech, Language, and Swallowing Disorders, Massachusetts General Hospital, Boston
|
| Dysphagia: ubiquitous, debilitating, life-altering, progressive, and never truly resolves; defined differently in different
clinical trials; sometimes defined as dietary grade level to which patient assigned (eg, whether patient on pureed diet or
on feeding tube, whether patient’s perception of swallowing problem is problem); sometimes, outcome measure weight
loss as measure of dysphagia or physician’s perception of patient’s difficulty; present before treatment in patients with tumor
affecting aerodigestive tract; also during and after treatment; range of dysphagia symptomatology 89%; compounded
by other toxicities, eg, trismus, xerostomia, odynophagia; multidisciplinary problem
|
| Aspiration: occurrence rate 70% to 80% in patients during treatment; silent aspiration—most common feature; patient
does not cough in response to amount of aspiration; probably underreported; substantial disparity between number of patients
who aspirate and number of patients who develop pneumonia; data not compelling about 1:1 link between aspiration
and aspiration pneumonia; question of how well patients tolerate aspiration if it occurs; also whether onset of disease matters
for outcome of swallowing; study—looked at 53 subjects (3 tumors in nasopharynx, 22 in oropharynx, larynx, hypopharynx,
and unknown primary); stage mostly T3 and T4 (some T2); treatment conventional radiation therapy in single
fractions; variety of regimens compared; patients measured at baseline and at 3 mo after treatment; found that for each site,
various biomechanical problems in swallow but no significant difference in functional swallows across sites; swallowing
impaired in similar fashion (whether tumor in nasopharynx or oropharynx); patients with laryngeal and hypopharyngeal tumors
more likely to aspirate large volumes; no difference in swallowing among different regimens; general consensus that
superior pharyngeal constrictors most sensitive to radiation therapy; shown that limiting dose to <50 Gy causes fewer
problems in swallowing; most patients particularly fearful about swallowing and sensation of choking after treatment; also
see thickening in prevertebral soft tissue of arytenoid cartilages and epiglottis; other problems include tongue base retraction,
problems elevating and closing larynx, and strictures; problems cause material to come out of nose, go down wrong
way, or stick in pharynx, causing multiple swallows; cervical esophageal strictures more recognized; dysphagia worsens
before improving (3-6 mo before patient develops new “normal”)
|
| G tubes: literature stating that if patient has nothing by mouth for ≈2 wk, long-term effect on swallowing decreases; effect
of putting G tubes on dysphagia unknown; not benign procedure, but prevents patient from being hospitalized and allows
treatment to continue in more interrupted fashion; pretreatment modified barium swallow study performed to identify potential
problems; patient seen 1 to 3 mo after treatment; management—team effort; important to know psychologic
makeup of patient; patient must be part of plan; set reasonable and attainable goals; teach patient how to choke safely;
have patient document progress; principles of treatment—include restoring physical integrity as far as possible and increasing
airway protection and swallowing efficiency; ultimate goal to remove feeding tube; recommended that patients
with submental edema (affects hyoid elevation and anterior movement) receive manual lymphatic drainage; TheraBite
used for patient with problems in pterygoid muscle and significant jaw hypomobility (important to do prophylactically);
xerostomia—common problem with IMRT; no effective solution; having something to drink while eating most helpful
solution; swallowing exercises—performed before, during, and after treatment; compliance poor; speaker advises patients
to swallow every day; ensure that pain control good and secretions removed; exercises helpful in changing geometry
and avoiding leaks in airway or at nose; videofluoroscopic or endoscopic swallowing evaluation only way to
determine what works; not all patients benefit from tucking chin
|
Suggested Reading
Chen MF et al: Radiotherapy of early-stage glottic cancer. analysis of factors affecting prognosis. Ann Otol Rhinol Laryngol
112:904, 2003; Forastiere AA et al: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal
cancer. N Engl J Med 349:2091, 2003; Ganly I et al: Postoperative complications of salvage total laryngectomy.
Cancer 103:2073, 2005; Ganly I et al: Results of surgical salvage after failure of definitive radiation therapy for early-stage
squamous cell carcinoma of the glottic larynx. Arch Otolaryngol Head Neck Surg 132:59, 2006; Hartl DM et al: Treatment
of early-stage glottic cancer by transoral laser resection. Ann Otol Rhinol Laryngol 116:832, 2007; Hinni ML et al:
Transoral laser microsurgery for advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg 133:1198, 2007; Langerman
A et al: Aspiration in chemoradiated patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 133:1289,
2007; Ljumanoviæ R et al: Supraglottic carcinoma treated with curative radiation therapy: identification of prognostic
groups with MR imaging. Radiology 232:440, 2004; Nomiya T et al: Advantage of accelerated fractionation regimens in definitive
radiotherapy for stage II glottic carcinoma. Ann Otol Rhinol Laryngol 115:727, 2006; Santos AB et al: Selective
neck dissection for node-positive necks in patients with head and neck squamous cell carcinoma: a word of caution. Arch Otolaryngol
Head Neck Surg 132:79, 2006; Taguchi T et al: Concurrent chemoradiotherapy with carboplatin and uracil-
tegafur in patients with stage two (T2 N0 M0) squamous cell carcinoma of the glottic larynx. J Laryngol Otol 120:478, 2006;
van den Broek GB et al: Pretreatment probability model for predicting outcome after intraarterial chemoradiation for advanced
head and neck carcinoma. Cancer 101:1809, 2004; Woodard TD et al: Life after total laryngectomy: a measure of
long-term survival, function, and quality of life. Arch Otolaryngol Head Neck Surg 133:526, 2007; Yilmaz T et al: Post-
operative radiotherapy in advanced laryngeal cancer: effect on local and regional recurrence, distant metastases and second primaries.
J Laryngol Otol 119:784, 2005.
|
