Treatments > Factors Influencing Treatment Decisions

Last update: 04/24/2013

TOPICS
Factors | When? | Which? | Goal of Treatment? | Big Picture Questions

Big Picture Questions and YOUR treatment priorities	Regarding the Clinical Context
Factors that determine treatment timing and approach	FDA Treatment Flow Chart for Indolent NHL
Considerations at relapse,  guidelines from patients	Treatment Resources
Background on treatment: goals | types | outcomes | interventions	Would a clinical trial be appropriate for me?  Questions for your doctor PDF
Questions for your Doctor	Watch & Wait - considerations for and against

TOPIC SEARCH: PubMed  Tweet

There are many factors that influence treatments decisions, particularly for patients with indolent lymphomas.  It's an ongoing and complex process, which involves understanding the risks of the disease and the potential risks and benefits of available treatment options.  ...   (discussion continued below)

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Factors that can influence the
timing and choice of therapy - the clinical context

The following table illustrates the complexity of the clinical context - how each case and lymphoma can be unique.  Thus treatment decisions need to be tailored accordingly - the reason professional guidance is required. 

Perspective on the Importance of the Clinical Context

Disease Characteristics	Basis of Treatment Decisions	Patient Characteristics
Type of lymphoma (cell type)  and it's expected natural history Grade: indolent, intermediate, aggressive Stage: localized or widespread? High or low-risk clinical behavior? Growth rate? Discordant - growing faster in one location than another?   Emerging in new locations?   Sensitivity to initial therapies?   Causing symptoms?  serious or mild? predictive of need to treat? Suggests high-risk disease? See FLIPI for a system of estimating  risk in follicular lymphoma   Previously treated or untreated? Types and toxicities of prior treatments Response of lymphoma to  treatments and treatment types?   Sensitivity to initial therapy Complete Response?   Partial Response?     Duration of response to last therapy? Stable Progressing during treatment?   Location of tumors Near vital organs?  Bone marrow involvement? Affecting appearance or social confidence? Bone marrow function (blood counts) Monitoring schedule for accurate assessment of disease status?	Goal of treatment:   a) Durable remission (potential to cure?)   versus   b)  Management - treat minimally as needed IMPORTANT: the most appropriate goal of therapy can be based on both Disease and Patient Characteristics, and not necessarily on patient preferences alone.   Strength of evidence for available therapies? Best Practice (standard of care)?   Large controlled randomized trials?   Long follow up?   Findings reproduced by different groups? Balancing potential benefits versus  risks (short and long term)    Proven to improve survival?   Can burn treatment bridges?   Fast acting? How different physicians may interpret the same data Physician biases when Best Practice is not established Treating physician is a lymphoma specialist or general oncologist? Treating physician is aware of clinical trials and willing to consider referral to clinical  trials? Treating physician can administer the full range of therapies? RIT?, Stem Cell Transplant? Clinical Trials? Large cancer center, versus community center Patient-physician communications Availability of tissue to determine eligibility for targeted therapy?	Age (chronological and physiological) Performance Blood counts Comorbidities (secondary conditions)?  Kidney (renal) and Liver (hepatic) function?   Diabetes? Heart condition? HIV/AIDS, Hepatitis, Autoimmune? Preferences/temperament Tolerance for risk? Note: Even inaction has risk; and depending on the circumstances, under-treating or delaying treatment can be higher risk than administering aggressive or immediate treatment. Prefers treatment that are easy to administer and least disruptive to normal life? Prefers treatment with curative potential? Will report symptoms  honestly and on a timely basis? Our biases, beliefs, and fears. Quality of life considerations:   significance of loss of hair,  fatigue, anxiety ... Life Circumstances Informed about disease, therapies and risks? Financial limitations? Insurance   Limited/ none? co-payment issues? Supportive care at home? Ability to travel? Responsibilities and duties to others: Employment  Family, children

GOAL OF TREATMENT

What is the most appropriate goal of treatment? 

Is it to achieve a durable remission with potential  to cure?
Or is it to manage the disease, treat with lower toxic therapies as needed?

Often the treatment goal is based on: 

1. risk of the disease - based on pathology results and clinical behavior FLIPI
   (rate of growth, sensitivity to treatments used so far)  
    

2. age - being young sometimes favoring, or allowing for, more aggressive approaches to therapy
    

3. strength of the data* that supports the goal of the treatment for your clinical setting: 
    
   a) the type of lymphoma (MALT, Follicular, MCL...)
    
   b) grade - indolent (slow growing/stable), or aggressive 
    
   c) stage - areas of involvement and tumor burden 
      (nodal, localized, extranodal, degree of bone marrow involvement), 
    
   d) treatment history and sensitivity to prior treatment types and duration of response to prior therapy (Complete response?  PR (partial response?), Progression during treatment?)
    
   * Note: Response to a biologic, such as Rituxan, may not predict response to chemotherapy, and vice versa.
    
   e) your performance and immune status, comorbidities (secondary conditions) 
    
   * Strength of Data:  Is best practice established?
       Proven superior in comparative studies? ... Large controlled randomized trials?
       Long follow up?  
       Reproduced by different groups? 
       

Regarding Tradeoffs

Virtually every treatment approach has potential tradeoffs:  

An aggressive therapy might give a better chance for a complete and more durable remission (or cure), but can have greater toxicities in the short or long term.  

However, if you take smaller risks with each treatment (less aggressive therapy), you may need to treat more often (depending on the clinical behavior of the lymphoma) and therefore the cumulative risk could be the same or greater with what seems to be the safer  protocol.

... And even avoiding or delaying therapy has potential risks.

So there's no avoiding risks, we just exchange one kind for another. 

This is not to suggest that any choice is as good as another in all clinical circumstances, only that in some instances a definitive best choice will not exist. And we will need the help of our doctors to sort this out.

The Challenge of indolent disease: 

The clinical course of the follicular (and other indolent) lymphomas can be quite variable. Some patients with widespread disease have no symptoms or signs of progression for years and do not require immediate therapy, while others cases demonstrate rapid tumor growth and need early treatment." Source towercancerfoundation.org/

So each case can be unique, which is a reason that there is no gold-standard approach to treating it; no definitive best practice.  Further, it takes time to get reliable answers from clinical trials, because survival is so long for the indolent lymphomas and the assessment of any one therapy is confounded by the use of other effective therapies when needed.  

"Ultimately, it may well be that the optimal treatment will be determined
by patient clinical and biological characteristics." ~ Dr. Bruce Cheson. Advances in the Treatment of Non-Hodgkin's Lymphoma - Dr. Cheson  Medscape

Can indolent lymphomas be cured?  
 
Only a minority of patients with advanced stage indolent lymphomas may be cured, but emerging data suggests that the proportion could be increasing.  
 
See Can we Cure Indolent Lymphomas?

Factors that Can Influence Timing of Therapy
for an Indolent Lymphoma?

	Is there an advantage to treating now, versus treating later? What is the preferred therapy when treatment is needed? A preference to manage the lymphoma might be reason to initiate treatment somewhat sooner with less toxic but also less potent therapies.
	What is the Clinical status and behavior of the lymphoma Such as sites of involvement, tumor burden, and clinical behavior - the growth rate. Is there a need to Treat - such as is the lymphoma causing symptoms?

Watch & wait (w&w) is the practice of observing the lymphoma carefully to monitor its behavior in order to treat it only as needed.  W&W became the standard approach for indolent lymphomas because earlier studies indicated that early interventions with combination therapies could lead to responses, but that those who were observed until therapy was needed did just as well in the long term (survival) without early exposure to the toxicity of treatments.   

Thus, "Careful observation without initiation of therapy is an appropriate option in the management of patients with relatively asymptomatic advanced non-Hodgkin's lymphomas of favorable histologic types." Watchful waiting is still common practice today. 

Click here for more detail on Watchful Waiting and Monitoring Lymphomas

Q: How long before I need treatment for indolent lymphoma?

The Time to initial treatment can vary significantly.

For follicular lymphoma "a substantial proportion of patients may never require treatment."  Source: Follicular lymphoma: a historical overview, Koen Van Besien & Harry Schouten. Feb 2007

In one study "the median (middle) time before requiring treatment was 31 months, and there have been 19 patients who have not yet required therapy for periods of 3 to 104 months.  ... 

The median actuarial survival for all 44 patients was 121 months (~10 years). 

Source: No initial therapy for stage III and IV non-Hodgkin's lymphomas of favorable histologic types, Source: PMID: 369420  Also see related related PubMed articles  PubMed 
 

Q: What are the signs and symptoms that may indicated when to treat indolent lymphomas?

	Symptoms (fatigue, pain, fevers...)
	Threatened end-organ function (enlarged node obstructing bowel)
	Cytopenia secondary to lymphoma (low blood counts)
	Bulky disease - according to the GELF criteria: nodal or extra-nodal mass (except spleen) > 7cm in its greater diameter 2
	Steady progression
	Patient preference
	Elevated serum LDH or B2-microglobulin
	involvement of multiple nodal sites (each with a diameter greater than 3  cm) 2
	symptomatic splenic enlargement 2
	compressive syndrome 2
	pleural/peritoneal effusion 2   Sources: http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf 1 PRIMA study: 2 http://prima. gela.org/ studydoc/ 1_ETUDE/PRIMA_ Protocol_ Version4. 0_Finalnonsurlig ne.pdf

See also: GELF criteria for need to treat.

Q: Is  indolent lymphoma ever treated early - before the need to treat?

Yes.  Stage I and II (localized) indolent lymphoma are typically treated at diagnosis with curative intent with localized radiotherapy. The cure rate is about 50% according to some reports. 

See for many published studies on this question: www.lymphomation.org

NOTE: You may want to ask your oncologist about use of PET and a bone marrow biopsy to confirm that the lymphoma is truly localized. "PET may be useful in confirming limited disease in the few patients with early stage I disease, because these patients may be treated with local radiation." Source jnm.snmjournals.org 
 

Q: What about managing lymphoma with herbs and alternative therapies?

It's easy to be seduced by testimonials made by individuals and groups claiming that natural life style changes can change the course of the disease, but, unfortunately, there is no clinical evidence to support these claims.  

See for details: When lay persons give medical advice & The Problem with Testimonials

SELECTION OF TREATMENT?

The good first step is to decide on the most appropriate goal of treatment ...

Is it to manage the disease by treating minimally as needed? 

or to achieve a durable remission with combination therapy?

Note: Selecting the goal of treatment and the protocol should be done in consultation with your oncologist, because he or she is a medical professional and has first-hand clinical information about your diagnosis, health status, treatment history, and the clinical behavior of the lymphoma. 

Getting a second opinion from a *lymphoma specialist* is strongly recommended. 

General community oncologists may not be up-to-date on the latest approaches to treating the many subtypes of lymphomas. Lymphoma specialists will also be aware of investigational approaches that have promise, such as new doses or combinations of proven therapies. Most general oncologists will encourage you to seek a second opinion and adopt the advise given by the specialist.

See also How to inquire about Trials?

Overview of Common Treatment Options for indolent lymphomas
 

	Watchful Waiting (W&W)   Judge clinical behavior and avoid treatment before it's needed. Some patients with indolent lymphomas (a minority) never need treatment.
	Intent to manage (first line)   Rituxan x 4, or Rituxan x 8 (extended dosing study) Single agent alkylators (Chlorambucil or Cyclophosphamide) or steroids
	Intent to manage (second line and subsequent therapy)   Rituxan x 4, or Rituxan x 8 (extended dosing) Single agent alkylators (Chlorambucil or Cyclophosphamide) Oral low dose combination chemotherapy, such as PEP-C
	Intent to induce durable remission (first line for localized disease)   localized radiotherapy (stage I or stage II)
	Intent to induce durable remission (first or second line)   Rituxan-based Chemo (R = Rituxan)          CHOP-R, CVP-R, F-R, , FND-R, Bendamustine+Rituxan Rituxan-based chemo, followed by extended dosing (maintenance) Rituxan Radioimmunotherapy (RIT) as single agent (study) RIT following combination chemotherapy (study)
	Intent to induce durable remission (second line and subsequent therapy)   Autologous stem cell rescue  Allogeneic stem cell transplant Radioimmunotherapy

Main source: NCCN Clinical Practice Guidelines in Oncology™ Non-Hodgkin's Lymphoma, 2008 http://www.nccn.org/professionals/physician_gls/PDF/nhl. pdf  (requires free registration)

 

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Factors that Influence the Type of Treatment

Factors that influence treatment timing and type - when the goal is management:
 

	Is a fast treatment response necessary?
	Is there a promising investigational or approved therapy with minimal expected side effects - to  try when treatment is not needed?
	How the therapy under consideration might complement or compromise subsequent  treatment options or eligibility for subsequent treatment protocols.
	The short - or long-term toxicity of the treatment under consideration.
	Tumor burden and disease locations.
	Other factors that determine your eligibility for treatments

Factors that influence treatment selection - when the goal is a durable remission :
 

	The disease - and treatment-specific data from well-designed studies that support the use of a treatment for your setting;
	The treatment-related risks compared to other treatments appropriate to this goal;
	Your age, general health, and tolerance for risk;
	Tumor burden and disease location;
	You have a family member who is a good match and is willing to donate stem cells;
	Other factors that determine your eligibility for treatments

Other factors that influence treatment timing and type:
 

	The disease - and treatment-specific data from well-designed studies that support the use  of a treatment for your setting;
	Your physician's areas of expertise and possible biases;
	If your physician works with investigational therapies;
	What your insurance carrier will pay for;
	The questions you ask, how well you communicate your treatment goals and symptoms,  and how informed you are about the disease and the available treatments.
	Other factors that may determine your eligibility for treatments: We recommend that you take an inventory of these items (that describe your treatment setting) to help the doctors you consult to more easily identify appropriate treatment protocols.    Diagnosis - lymphoma subtype (including phenotype markers, such as CD20, CD19, etc.)  Treatment history - specific prior therapies or treatment types - may be required, or may exclude you Bone marrow involvement with lymphoma (greater than 25% bilaterally for Bexxar/Zevalin)  Bone marrow (Hematopoietic) function - measured by Hemoglobin, Lymphocytes, Platelets,  Neutrophils   Co-morbidities - other conditions, such as heart (cardiovascular) disease, HIV, Hepatitis B/C,  and other infections  Kidney (Renal) function - measured by Creatinine Liver (Hepatic) function - measured by Bilirubin, AST and ALT  Lungs (Pulmonary) function - measured by a variety of tests or observation  Neurological - such as history of seizures, CNS involvement   Patient characteristics - age, gender, life expectancy, pregnancy, etc.  Performance status - as measured by performance standards

Regarding the Clinical Context

"If treatment for cure is necessary; is it possible? If possible, is it necessary?"
~ Dr Willet Whitmore (on prostate cancer)

Dr. Whitmore’s assessment seems to apply pretty well to the indolent lymphomas and CLL. However, for most types of indolent lymphomas treatment is eventually (but not always) needed. So there are two basic approaches to clinical care and research.

1) One being to manage it with treatments that have lower toxicity - and only as needed.

- With this objective it can be argued that one should treat earlier (when the need to treat is not evident but expected soon) in order to have a better chance for the less aggressive therapies to be effective - but also because milder therapies generally are not as fast-acting and advanced lymphoma can sometimes require a timely response.

2) The second goal is to treat the indolent lymphoma with intent to induce a durable remission (and dare we say it, with a potential for cure) with more aggressive combination therapy.

- Here treatment is generally deferred to when the need for treatment is clearly indicated. However, waiting until the condition becomes too advanced (bulky, causing symptoms) can sometimes limit therapeutic options and lower the odds of achieving the best results.

Which approach is best?

It's sometimes argued that it's better to conserve one's "bullets" to preserve future options. However, achieving a long remission could increase your options - allowing you to use even the same therapy again when therapy is needed -- and that this might better preserve therapeutic options and lead to less treatment resistance compared to using milder therapies more often.

So this is a big reason why --- for the indolent lymphomas --- there is NO standard of care - no easy, one-size-fits-all formulas for how and when to treat.

So informed choice is a process, which requires an objective understanding of our clinical context:

1) The natural history - or anticipated clinical course for your type of lymphoma,

2) The potential benefits and risks of the current standards of care, such as can it cure?

3) An appreciation of the unique and sometimes changing individual risk factors - such as one's age and performance, the changing behavior of the lymphoma, or responsiveness to prior therapies - and how long the response lasted.

The clinical context can influence how much risk is appropriate to take when treating the lymphoma and also how appropriate it might be to ask about and consider clinical trials.

Finally, these are difficult decisions and there will usually be uncertainty. 

Even with known drugs there is an unknown of how they will affect us as individuals.
And so it is a bit scary. Hopefully, you will get started soon and
will get good results that show that treatment can make you feel better.
~ Andy (webmagjc)

Karl Schwartz
President, PAL

Resources  

1. The role of anthracyclines in combination chemotherapy for the treatment of follicular lymphoma: retrospective study of the Intergruppo Italiano Linfomi on 761 cases. Leuk Lymphoma. 2003 Nov; 44(11): 1911-7. PMID: 14738142 | Related articles 

2. Grade 3 and anthracycline-containing [such as CHOP] treatments 
   Commentary from Experts  PAL 
    
   Meet the Professors - a provocative discussion among experts regarding first 
   treatment options for advanced follicular lymphoma  meettheprofessors.com  | PDF

3. Controversies in Follicular Lymphoma: "Who, What, When, Where, and Why?"  
   
   Myron S. Czuczman Hematology 2006:303-310. Abstract | Full Text | PDF

4. Webcast: Attacking NHL Early   

5. Follicular lymphoma: chemotherapy and/or antibodies?
   
   Michele Ghielmini  Oncolog Institute of Southern Switzerland  www.bloodjournal.org

6. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma.
   
   J Clin Oncol. 2002 Oct 15;20(20):4261-7. PMID: 12377971 | Related articles 

7. Leonard, John, MD  * (Highly recommended) 
   
   Making Decisions about Treatment for NHL LLS PDF (8/9/05)

8. NCCN Practice Guidelines in Oncology (NHL) – v.1.2008  
   http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf 

9. Approaches to treating non-Hodgkin's Lymphoma:
   
   Dr Leonard  nhlupdate  |  Dr Coleman  nhlupdate  |  Dr Zelenetz nhlupdate
   
   Dr. Cheson  nhlupdate |  Dr Czuczman  nhlupdate.com |  Dr Armitage  nhlupdate.com
   
   Audio files for patients: John Leonard, Mitchell Smith, Brad Kahl  nhlupdate.com

10. High-Dose Therapy for Follicular Lymphoma Revisited: Not If, but When? -  Journal of Clinical Oncology, Vol 21, Issue 21 (November), 2003: 3894-3896  www.jco.org 

11. Background Information on Non-Hodgkin's Lymphoma, FDA  PDF  | PDF-Help

12. Cancer Treatment: Determining the Best Long-Term Plan for You  PDF file - Maloney, Cha | PDF Help

13. Conventional Treatments of indolent NHL,  Cheson / Zelenitz  Transcript or  Webcast |  WebCast-help 

14. Current Therapies in the Treatment of Non-Hodgkin's Lymphoma: Chemotherapy
    
    Richard I. Fisher, MD - Medscape (free login req.) - ** Comprehensive **

15. "Thin" Decisions  Patient perspective on consulting experts and making treatment decisions

16. Treatments of NHL (flowcharts) - MDACC  PDF | PDF-Help

17. NCCN Clinical Practice Guidelines in Oncology™ Non-Hodgkin's Lymphoma, 2008 http://www.nccn.org/professionals/physician_gls/PDF/nhl. pdf 

18. Indolent, Stage I and Contiguous Stage II Adult Non-Hodgkin’s Lymphoma ~ Best Practice  Cancer.gov

19. Indolent, Recurrent Adult Non-Hodgkin’s Lymphoma ~ Best Practice  Cancer.gov

20. Indolent, Noncontiguous Stage II/III/IV Adult Non-Hodgkin’s Lymphoma ~ Best Practice  Cancer.gov 

21. How I treat indolent lymphoma  bloodjournal.hematologylibrary.org

    Dr. John G. Gribben  Institute of Cancer, Barts and The London, Queen Mary School of Medicine, London, United Kingdom

22. Indolent, Recurrent Adult Non-Hodgkin’s Lymphoma ~ Best Practice  Cancer.gov

23. Dan L. Longo, MD, Scientific Director
    National Institute on Aging Baltimore, Maryland 

    Follicular Lymphoma: Expanding Therapeutic Options  Cancernetwork.com

24. Aiming at a Curative Strategy for Follicular Lymphoma caonline.amcancersoc.org  
    Maurizio Bendandi,MD, PhD   http://caonline.amcancersoc.org:80/cgi/reprint/58/5/305?eaf  

25. R-CHOP versus R-CVP in the treatment of follicular lymphoma: a meta-analysis and critical appraisal of current literature  pubmedcentral.nih.gov

Also see Expert Review Articles and Interviews

* Considerations for the younger patient with indolent lymphoma:  

The goal of aggressive therapy is to get a durable response, and a possible cure. It may be that the aggressive approach is more reasonable for the young patient, especially if it's determined that you have high-risk disease. 

First, initial treatment provides the best opportunity to succeed - there is less tumor burden, and your health and the disease have not been affected adversely by prior treatments. For example, cancer cells can adapt from multiple exposures to single agent treatments, which can lead to more resistant disease later on.

Second, younger persons can often rebound better from the toxicities of strong treatment - and therefore may not be harmed as much long term, even if the treatment fails to meet the goal. And if you fail to realize a durable remission, you will have learned early that you have high risk disease and can adapt the clinical plan accordingly.

Finally, if the treatment succeeds, you may improve survival significantly - which is especially important to young patients who will reach survival expectations when still young. (Current estimates for survival ranging from 7 to 18 years for follicular lymphoma, depending in part on the age of the population.)   

* Considerations for the elderly or Infirm patient with indolent lymphoma:  

Watchful waiting?

Rituxan, and single agent chemotherapy for management?

Radioimmunotherapy  instead of combination chemotherapy?

 

In conclusion, when first diagnosed with indolent lymphoma ... 

... we suggest the following: 

1. Try to objectively identify the risks of the disease by tests and close observation
   
   (How fast the lymphoma progresses or how well it responds to initial management treatments).  

2. Become informed about the disease and its treatments. 

3. Consult respected experts to discuss the risks and benefits of all standard treatments, 
   and promising investigational options. 

4. Communicate your priorities and fears to your doctors. 

5. Honestly report symptoms to your doctor.

6. Consult with a specialist to determine the most appropriate goal of treatment - and the approach and timing that best fit the goal.

7. Also ask about the impact of the protocol under consideration on future treatment options.

Conflict of Interest in Medical Decision-making?

Sometimes.  But rarely is it unethical.  See for details: PAL

Why should patients consult outside experts and become informed?  
 
Even trained oncologists can have conflicts of interest, biases, or gaps in knowledge - especially if he or she does not specialize in lymphomas. 

Investigators may have an intellectual bias about an investigational therapy they are testing.  A community doctor might have a bias in favor of what is easiest to administer.  

An HMO physician may prescribe what is least expensive. Another doctor might be influenced, unconsciously or not, by sales promotions from the drug industry.  

Patients expressing their desire to continue working without interruption may influence a busy physician to prescribe what meets the immediate needs, without fully discussing possible negative long-term implications of that treatment decision ...   

Still another reason to seek a second opinion is that it sets up a kind of peer review, which is likely to be an incentive for your local community doctor to be more focused on your care and the decision process. The good community doctor will encourage a second opinion by experts, and will be willing to carry out the recommendations, when possible ... or send you elsewhere when not.

We suggest that you avoid the following:  

1. Start a treatment without first consulting at least one lymphoma expert - unless symptoms or clear dangers indicate a strong need to treat, and you are comfortable with the rationale. 

2. Base your treatment decision on the outcomes of other patients. Keep in mind that each lymphoma and patient can be unique.

3. Believe conspiracy theories used to promote unorthodox therapies. Consider that these theories require the complicity of multiple scientists, doctors, and regulators - who also get cancer and whose loved ones, spouses, parents, grandparents and children also get cancer.   

Strive to be objective: see Evaluating Medical Claims and Data.

Big Picture Questions 
 
... when it's time to make a treatment decision

Our Focus is on Clinical Trials
 

7 Reasons to Consider Trials
based on our
clinical circumstances PDF

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Seven big-picture questions that help to guide the most appropriate approach to treatment

·         Question 1: What is the natural history of the disease?
(Aggressive, indolent or slow growing, variable)

The likely clinical course can determine the approach or goal of therapy.  For example, for aggressive lymphomas the most appropriate goal of therapy is usually to cure.  For lymphomas with a variable clinical course a period of observation might be needed to judge its behavior.

·         Question 2: What are my individual risk factors?
(age, general health, secondary conditions)

Such factors can influence the goal or approach to therapy.  For example, if we are frail a modified protocol or a clinical trial might be more appropriate than standard therapy.

·         Question 3: How effective is the standard approach? 
(Curative, highly effective, variable, unsatisfactory)

This can often determine if a clinical trial should be considered.  For example, if the lymphoma is not likely to be cured with standard therapy and the natural history is aggressive, a clinical trial might be the most appropriate choice.

·         Question 4: What is the Goal (or approach) of Therapy?
(cure, durable remission, management, palliative)

The most appropriate approach or goal of treatment is often based on answers to questions 1, 2, 3.  For example, if the natural history indicates that cure is unlikely with standard therapy, and the clinical course is indolent, treating as needed to manage the condition  with lower toxicity could be the most appropriate choice.

·         Question 5: What’s the Level of Evidence for the proposed therapy?
(be it standard or investigational)

What clinical trial results have been reported for patients with my diagnosis and clinical circumstance?   Were the studies large enough?  Did they have controls (randomized) or where they single-arm studies?

Is there consensus about the best approach?
What are the known risks and potential benefits for the recommended therapy? What are the key tradeoffs in a close call?

·         Question 6: When should I start treatment?
(based on answers to questions 1, 2, 3, 4)

The natural history of the lymphoma can determine how soon treatment is needed.  For example, if indolent, close observation without treatment (watch and wait) can be appropriate or recommended. 

·         Question 7: How do my personal priorities enter into the decision?   

On this question YOU are the expert!

In situations where there is a close call (where more than one approach is reasonable), I prefer a treatment that:

	Is most likely to help my symptoms to resolve quickly
	Provides the best chance for a cure   I will accept certain long term toxicities if there is a chance for cure?
	Has the least risk of death
	Has the lowest short term risks and fewest side effects
	Will be the least disruptive to my normal life, such as can be administered at home
	Will have the least negative impact on my quality of life
	Is most likely to be the best approach in the long term (if known).