Treatments > Factors that Influence Treatment Decisions

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, as well as assessing the potential risks and benefits of numerous treatment options.  ...   (continued below)

Summary of factors that can influence timing and choice of therapy

The purpose of this "inventory" of factors is to show the complexity of treatment decisions - and how they can interact; and how each case and lymphoma can be unique, thus treatments may need to be tailored accordingly.

Job one: determine the most appropriate goal of treatment. 

Durable remission with potential  to cure?
versus  Management - treat minimally  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* 
               (Complete response?  PR (partial response?), Progression during treatment?)
                * Response to a biologic, such as Rituxan, may not predict response to chemotherapy.
           e) performance status, immune status, comorbidities (secondary conditions)  ....   
   
   * Best Practice established)? |  Large controlled randomized trials? |  Long follow up?  | Reproduced by different groups? 

The problem of indolent disease: 

There is no standard approach. No best practice. Each case is unique. It can remain dormant for many years, or progress and behave aggressively.  Typically, indolent lymphomas are sensitive to initial therapies. 

It takes time to get reliable answers from clinical trials, because survival is long for indolent lymphomas, and the clinical course of individual patients is variable.  

"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 may be increasing.  
 
See Can we Cure Indolent Lymphomas?

When to treat? 

Watch & wait (observation until symptomatic) became the standard approach for indolent lymphomas because studies (circa 1979) indicated that early interventions with combination therapies did not provide a survival advantage.   

"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." PMID: 369420

Watchful waiting is still common practice today. Click here for more detail.

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

Q: Is  indolent lymphoma ever treated early?

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? 

* 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 get a CR (complete response), 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 12 years.)   

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

Rituxan, and single agent chemotherapy for management.

Radioimmunotherapy may be considered 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 specialist to determent 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.

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. 

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.

Rank Your 
Treatment Priorities

Using the items on the right, create a list of your treatment priorities, most important first. 
(The current order is random.)

When it's time to treat, this ranking list may help you decide on the treatment that's best for you. 

These priorities are primarily for indolent (slow growing) lymphoma.

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 The treatment:

Big Picture Questions

Good questions to ask your doctor when reviewing treatments

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When it comes time to make a treatment decision, Dr. Maloney at the October 2002 Education Forum sponsored by LRF offered the following rational  guidelines. 

First treatment as Assessment - A Boxing Analogy

One way to look at watchful waiting is as an assessment period. Like what prize fighters do in the early rounds as they circle one another. That is, it's a time to size up the opponent to determine how to proceed. Is my opponent fast or slow? Do I need to take a chance early, or is he so docile that I need not take any risks at all?  

Similarly, the response to first treatment, like a probing jab, is also part of the assessment. It provides clues about how to proceed. Is my opponent strong or weak, susceptible to damage,  or is he hard as nails?

(But be aware that lack of sensitivity to Rituxan does not predict sensitivity to chemotherapy, and probably vice versa, because they these agents have completely different mechanisms of action. So a single agent chemotherapy might be tried after a round of Rituxan, for example, as part of assessment and hopefully it will be a successful action as well.) 

If both types of probing treatments fail to provide a significant benefit, it may be time to plan for tougher later rounds, such as by harvesting stem cells when the circumstance allows.  It may also be to time to consider taking risks in order to try to eliminate, instead of manage, your opponent. 

As always, timing's important - that is, when to expend your limited resources. You may want to wait for signs that your opponent is weak, or induce weakness by sequencing your offensive efforts with different combinations. 

But you also need to rest and recover in order to prepare for later rounds. So watchful waiting can be a time to take proactive action build and improve your general health and performance. 

Finally, when you are young and in good health it might be reasonable to start aggressively as you will being young and fit you may be better able to recover for the later rounds if needed.  In general starting aggressively, early, can be the best opportunity to win the fight outright, or improve your chances in the later rounds if you achieve  a durable remission. But this does not mean that you execute the plan before the opponent makes the first move ... is clearly on the offensive.