Treatment algorithm

Your Organizational Guidance

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Kanker van de mondholte: diagnose, behandeling en follow-upPublished by: KCELast published: 2015Cancers de la cavité buccale : diagnostic, traitement et suiviPublished by: KCELast published: 2015

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

Human papillomavirus (HPV)-negative

1st line – radiation alone or surgery alone

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ACUTE
|
Human papillomavirus (HPV)-negative
|
T1/T2, N0, M0 (early stage disease)
1st line – 

radiation alone or surgery alone

Patients may be treated with either upfront surgery or radiation.[2]​ Even though no randomized study has compared the two modalities, retrospective studies reported similar local control and survival rates, ranging from 80% to 90%.[57][75][76] The choice of treatment modality is dependent on size of the primary tumor and location within the oropharynx. Tumors at or approaching the midline (ie, tumors in the base of the tongue, posterior pharyngeal wall, soft palate, and tonsil invading the tongue base) are at risk of contralateral metastasis and warrant bilateral treatment.[2]

Historically, surgery for oropharyngeal cancer required splitting of the mandible or a pharyngotomy to provide access to the inferior tonsillar fossa or base of tongue.[Figure caption and citation for the preceding image starts]: Large base of tongue tumor not amenable to transoral robotic surgery, required open transhyoid approach to the base of tongueFrom the collection of Dr Linda X. Yin; used with permission [Citation ends].com.bmj.content.model.Caption@62462e0a[Figure caption and citation for the preceding image starts]: Transhyoid open approach to a large base of tongue tumorFrom the collection of Dr Linda X. Yin; used with permission [Citation ends].com.bmj.content.model.Caption@e1a9471

Transoral robotic surgery (TORS) is an innovative technique for early-stage oropharyngeal cancer that allows sparing of the mandible compared with conventional surgery.[82][Figure caption and citation for the preceding image starts]: Robotic wide-field tonsillectomy using the Da Vinci SP robotFrom the collection of Dr Linda X. Yin; used with permission [Citation ends].com.bmj.content.model.Caption@1e7d68eb[Figure caption and citation for the preceding image starts]: Robotic base of tongue resection using the Da Vinci SP robotFrom the collection of Dr Linda X. Yin; used with permission [Citation ends].com.bmj.content.model.Caption@2830b66

Preliminary results are promising; however, more data are warranted.[83][84]​ TORS is widely thought to be associated with significantly better postoperative functional outcomes, related to speech, swallowing, and need for tracheostomy.

When using radiation, the National Comprehensive Cancer Network (NCCN) recommends intensity-modulated radiation therapy to minimize damage to critical structures.[2]

1st line – surgery + postoperative radiation ± chemotherapy

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ACUTE
|
Human papillomavirus (HPV)-negative
|
T1-T2, N1-N3, M0; T3-T4a, N0-N3, M0 (locally advanced and resectable)
1st line – 

surgery + postoperative radiation ± chemotherapy

Resectable locally advanced oropharyngeal cancer can be treated with either surgery followed by postoperative radiation with or without chemotherapy, or by concurrent chemoradiation, with equal outcome. One randomized study of locally advanced head and neck cancer demonstrated similar local control and survival by either modality.[77] Even though the number of patients with oropharyngeal cancers was small, the study corroborated the equal effectiveness of both modalities reported in retrospective studies.[85][86][87]​ Survival ranges from 50% to 60% at 3-5 years because of the high rate of distant metastases (20% to 40%).[77][85][86][87][88]

When using radiation, the NCCN recommends intensity-modulated radiation therapy to minimize damage to critical structures.[2] 

Cisplatin is the preferred postoperative chemotherapy regimen in these patients.[2]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

1st line – chemoradiation

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ACUTE
|
Human papillomavirus (HPV)-negative
|
T1-T2, N1-N3, M0; T3-T4a, N0-N3, M0 (locally advanced and resectable)
1st line – 

chemoradiation

Resectable locally advanced oropharyngeal cancer can be treated with either surgery followed by postoperative radiation with or without chemotherapy, or by concurrent chemoradiation. One randomized study of locally advanced head and neck cancer demonstrated similar local control and survival by either modality.[77] Even though the number of patients with oropharyngeal cancers was small, the study corroborated the equal effectiveness of both modalities reported in retrospective studies.[85][86][87] Survival ranges from 50% to 60% at 3-5 years because of the high rate of distant metastases (20% to 40%).[77][85][86][87][88]​​ The benefit of adding chemotherapy to radiation has been reported by one meta-analysis for all head and neck cancer anatomic sites. Patients with oropharyngeal cancers had an 8.1% improvement in survival at 5 years.[89]​ Cisplatin is the preferred first-line chemotherapy agent given concurrently with radiation.[2][90]

When using radiation, the NCCN recommends intensity-modulated radiation therapy to minimize damage to critical structures.[2] 

Concurrent chemoradiation can be given without or following induction chemotherapy depending on the medical oncologist's preference.[2]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

1st line – chemoradiation

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ACUTE
|
Human papillomavirus (HPV)-negative
|
T4b, any N, M0 (locally advanced and unresectable)
1st line – 

chemoradiation

Randomized studies demonstrate better survival and local control with concurrent therapy than with radiation therapy alone.[2][91][92][93][94][95][96][97][98]​​​

The general standard of care is platinum-based chemotherapy concurrent with radiation ± adjuvant chemotherapy, where adjuvant chemotherapy would be given after the course of chemoradiation.

The standard chemoradiation regimen is high-dose cisplatin every 21 days concurrent with radiation, although poor performance status patients may require low-dose weekly cisplatin or carboplatin.[100] Optimal chemoradiation regimen remains unclear, as these regimens have not been directly compared. US physicians tend to use cisplatin and European physicians tend to use carboplatin.

When using radiation, the NCCN recommends intensity-modulated radiation therapy to minimize damage to critical structures.[2] 

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

1st line – induction chemotherapy + radiation or chemoradiation

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ACUTE
|
Human papillomavirus (HPV)-negative
|
T4b, any N, M0 (locally advanced and unresectable)
1st line – 

induction chemotherapy + radiation or chemoradiation

Another option is triple-drug induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by concurrent chemoradiation with weekly cisplatin or carboplatin.[2][99] The addition of docetaxel to induction cisplatin and fluorouracil resulted in a median survival of 71 months compared with 30 months for induction cisplatin and fluorouracil followed by concurrent chemoradiation. Local control was also superior in the triple-drug induction arm, although more hematologic toxicity was reported. One meta-analysis confirmed the superiority of the triple induction regimen.[101] However, the optimal chemoradiation regimen remains unclear, as these regimens have not been directly compared. 

When using radiation, the NCCN recommends intensity-modulated radiation therapy to minimize damage to critical structures.[2] 

See local specialist protocol for dosing guidelines.

Primary options

docetaxel

and

fluorouracil

and

cisplatin

-- AND --

cisplatin

or

carboplatin

1st line – immunotherapy ± chemotherapy

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ACUTE
|
Human papillomavirus (HPV)-negative
|
any T, any N, M1 (distant metastases at presentation)
1st line – 

immunotherapy ± chemotherapy

Should be treated with targeted therapy if amenable, and chemotherapy if not amenable to targeted therapy. Consideration should be given to combination therapy of immunotherapy plus platinum-based chemotherapy in the setting of metastatic head and neck cancer, as this has been shown to provide a survival benefit.[78]

The immune checkpoint inhibitor pembrolizumab is approved in the US as first-line treatment of metastatic or unresectable, recurrent head and neck squamous cell carcinoma in adults in combination with platinum chemotherapy and fluorouracil, or as a single agent in those whose tumors express PD-L1 with a combined positive score (CPS) ≥1. It is also approved in the US as a single agent for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with disease progression, on or after platinum-containing chemotherapy. The NCCN supports these recommendations.[2]​ In Europe, pembrolizumab is approved, as a single agent or in combination with platinum chemotherapy and fluorouracil, as first-line treatment of metastatic or unresectable, recurrent head and neck squamous cell carcinoma in adults whose tumors express PD-L1 with a CPS ≥1. It is also approved in Europe as a single agent for the treatment of recurrent or metastatic head and neck squamous cell carcinoma in adults whose tumors express PD-L1, with a ≥50% tumor proportion score and progressing on, or after, platinum chemotherapy. The approvals were based on results from the KEYNOTE-048 trial.[102]

Conventional chemotherapy is usually a platinum agent with fluorouracil.

See local specialist protocol for dosing guidelines.

Primary options

pembrolizumab

OR

pembrolizumab

-- AND --

cisplatin

or

carboplatin

-- AND --

fluorouracil

HPV-positive

1st line – radiation alone or surgery alone

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ACUTE
|
HPV-positive
|
T0-T2, N0 or N1 (<3cm lymph node), M0 (early stage disease)
1st line – 

radiation alone or surgery alone

Less-intense treatment may be adequate for HPV-positive oropharyngeal cancers.[2]​ Patients may be treated with either radiation or upfront surgery.[2] Even though no randomized study has compared the two modalities, retrospective studies reported similar local control and survival rates, ranging from 80% to 90%.[57][75][76]​ The choice of treatment modality is dependent on size of the primary tumor and location within the oropharynx. Tumors at or approaching the midline (ie, tumors in the base of the tongue, posterior pharyngeal wall, soft palate, and tonsil invading the tongue base) are at risk of contralateral metastasis and warrant bilateral treatment.[2]

Historically, surgery for oropharyngeal cancer required splitting of the mandible or a pharyngotomy to provide access to the inferior tonsillar fossa or base of tongue.[Figure caption and citation for the preceding image starts]: Large base of tongue tumor not amenable to transoral robotic surgery, required open transhyoid approach to the base of tongueFrom the collection of Dr Linda X. Yin; used with permission [Citation ends].com.bmj.content.model.Caption@144baf9[Figure caption and citation for the preceding image starts]: Transhyoid open approach to a large base of tongue tumorFrom the collection of Dr Linda X. Yin; used with permission [Citation ends].com.bmj.content.model.Caption@1deda488

TORS is an innovative technique for early-stage oropharyngeal cancer that allows sparing of the mandible compared with conventional surgery.[82][Figure caption and citation for the preceding image starts]: Robotic wide-field tonsillectomy using the Da Vinci SP robotFrom the collection of Dr Linda X. Yin; used with permission [Citation ends].com.bmj.content.model.Caption@770bac9c[Figure caption and citation for the preceding image starts]: Robotic base of tongue resection using the Da Vinci SP robotFrom the collection of Dr Linda X. Yin; used with permission [Citation ends].com.bmj.content.model.Caption@5c03d2bb

Preliminary results are promising; however, more data are warranted.[83][84]​ TORS is widely thought to be associated with significantly better postoperative functional outcomes, related to speech, swallowing, and need for tracheostomy. Moreover, with HPV-positive patients presenting with better functional status and having better survival, surgery-first approaches are often considered with the idea that radiation, as a treatment modality, may be reserved for a future recurrence. In addition, these patients have longer to live with the late effects of radiation therapy.

When using radiation, the NCCN recommends intensity-modulated radiation therapy to minimize damage to critical structures.[2] 

1st line – surgery + postoperative radiation ± chemotherapy

Back
ACUTE
|
HPV-positive
|
T3/T4 or presence of nodal disease beyond single lymph node <3 cm (early stage disease or locally advanced and resectable)
1st line – 

surgery + postoperative radiation ± chemotherapy

Resectable locally advanced oropharyngeal cancer can be treated with either surgery followed by postoperative radiation with or without chemotherapy, or by concurrent chemoradiation, with equal outcome.

When using radiation, the NCCN recommends intensity-modulated radiation therapy to minimize damage to critical structures.[2] 

Cisplatin is the preferred postoperative chemotherapy regimen in these patients.[2]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

1st line – chemoradiation

Back
ACUTE
|
HPV-positive
|
T3/T4 or presence of nodal disease beyond single lymph node <3 cm (early stage disease or locally advanced and resectable)
1st line – 

chemoradiation

Resectable locally advanced oropharyngeal cancer can be treated with either surgery followed by postoperative radiation with or without chemotherapy, or by concurrent chemoradiation. The benefit of adding chemotherapy to radiation has been reported by one meta-analysis for all head and neck cancer anatomic sites. Patients with oropharyngeal cancers had an 8.1% improvement in survival at 5 years.[89]​ Cisplatin is the first-line chemotherapy agent given concurrently with radiation.[2][90]​​

When using radiation, the NCCN recommends intensity-modulated radiation therapy to minimize damage to critical structures.[2]

Concurrent chemoradiation can be given without or following induction chemotherapy depending on the medical oncologist's preference.[2]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

1st line – immunotherapy ± chemotherapy

Back
ACUTE
|
HPV-positive
|
any T, any N, M1 (distant metastases at presentation)
1st line – 

immunotherapy ± chemotherapy

Should be treated with targeted therapy if amenable, and chemotherapy if not amenable to targeted therapy.​ Consideration should be given to combination therapy of immunotherapy plus platinum-based chemotherapy in the setting of metastatic head and neck cancer, as this has been shown to provide a survival benefit.[78]

The immune checkpoint inhibitor pembrolizumab is approved in the US as first-line treatment of metastatic or unresectable, recurrent head and neck squamous cell carcinoma in adults in combination with platinum chemotherapy and fluorouracil, or as a single agent in those whose tumors express PD-L1 with a combined positive score (CPS) ≥1. It is also approved in the US as a single agent for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with disease progression, on or after platinum-containing chemotherapy. The NCCN supports these recommendations.[2] In Europe, pembrolizumab is approved, as a single agent or in combination with platinum chemotherapy and fluorouracil, as first-line treatment of metastatic or unresectable, recurrent head and neck squamous cell carcinoma in adults whose tumors express PD-L1 with a CPS ≥1. It is also approved in Europe as a single agent for the treatment of recurrent or metastatic head and neck squamous cell carcinoma in adults whose tumors express PD-L1, with a ≥50% tumor proportion score and progressing on, or after, platinum chemotherapy. The approvals were based on results from the KEYNOTE-048 trial.[102]

Conventional chemotherapy is usually a platinum agent with fluorouracil.

See local specialist protocol for dosing guidelines.

Primary options

pembrolizumab

OR

pembrolizumab

-- AND --

cisplatin

or

carboplatin

-- AND --

fluorouracil

ONGOING

recurrent disease

1st line – surgery, radiation therapy, or chemoradiation (depending on initial therapy and location and extent of recurrent disease)

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ONGOING
|
recurrent disease
1st line – 

surgery, radiation therapy, or chemoradiation (depending on initial therapy and location and extent of recurrent disease)

For recurrent disease after previous local therapy without any evidence of distant metastases, salvage with surgery, radiation, or chemoradiation may be considered on an individual basis, while bearing in mind treatment toxicity.[105][106]

When using radiation, the NCCN recommends intensity-modulated radiation therapy to minimize damage to critical structures.[2] 

1st line – immunotherapy ± chemotherapy

Back
ONGOING
|
recurrent disease
1st line – 

immunotherapy ± chemotherapy

Patients with recurrent disease after definitive treatment should undergo salvage treatment with immunotherapy if they are not a candidate for surgery or chemoradiation. Consideration should be given to combination therapy of immunotherapy plus platinum-based chemotherapy in the setting of recurrent head and neck cancer, as this has been shown to provide a survival benefit.[78]

The immune checkpoint inhibitor pembrolizumab is approved in the US as first-line treatment of metastatic or unresectable, recurrent head and neck squamous cell carcinoma in adults in combination with platinum chemotherapy and fluorouracil, or as a single agent in those whose tumors express PD-L1 with a combined positive score (CPS) ≥1. It is also approved in the US as a single agent for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with disease progression, on or after platinum-containing chemotherapy. The NCCN supports these recommendations.[2]​ In Europe, pembrolizumab is approved, as a single agent or in combination with platinum chemotherapy and fluorouracil, as first-line treatment of metastatic or unresectable, recurrent head and neck squamous cell carcinoma in adults whose tumors express PD-L1 with a CPS ≥1. It is also approved in Europe as a single agent for the treatment of recurrent or metastatic head and neck squamous cell carcinoma in adults whose tumors express PD-L1, with a ≥50% tumor proportion score and progressing on, or after, platinum chemotherapy. The approvals were based on results from the KEYNOTE-048 trial.[102]  

The regimens described above are the preferred regimens, but there are many other recommended options. See local specialist protocol for dosing guidelines.

Primary options

pembrolizumab

OR

pembrolizumab

-- AND --

cisplatin

or

carboplatin

-- AND --

fluorouracil

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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