Harrisonâ��s reports that in 2004, approximately 173,000 new cases of lung cancer of all types were diagnosed in the US, 93,000 in men, 80,000 in women. Fully 90% of all cases occur in current or former smokers, so it remains a largely preventable disease. (1)
Though rates in males have declined in recent years largely due to aggressive anti-smoking campaigns, incidence in women has increased rapidly. Today lung cancer is the leading cancer killer in both sexes, surpassing even breast cancer in women. Despite widely promoted early detection campaigns, public awareness of the disease and advances in treatment approaches, only 14% of patients survive five years. As Minna writes in Harrisonâ��s, â��Thus, primary carcinoma of the lung is a major health problem with a generally grim prognosis.â��
Pathologists divide lung cancer into two major categories, small cell carcinoma and the non-small cell variants which include squamous carcinoma, adenocarcinoma, large cell carcinoma and bronchoalveolar carcinoma. Small cell and squamous cell most clearly relate to cigarette smoking, large cell less so. Adenocarcinoma, the most common of the lung cancers, accounts for approximately 40% of all cases, large cell, the rarest, affects only 15% of patients. (2) Small cell carcinoma responds best to chemotherapy and/or radiation, the non-small cell carcinomas far less so â�� though few survive five years in either group. In the conventional medical world, surgical resection of localized disease remains the best chance for long term survival, whatever the subtype.
Patient FV: A 3-Year Survivor
Patient FV is a 63-year old man with a history of myasthenia gravis diagnosed in 1993, which forced him to retire from his high stress profession. Since then, his myasthenia has waxed and waned, with exacerbations treated with Tensilon.
In June 2003, while playing tennis, he developed significant shortness of breath. At a local emergency room, a chest x-ray showed several pleural-based densities in the left lung and a CT scan revealed several nodular lesions in the left chest pleura up to 2 cm in diameter. Posterior pleural thickening was also noted, thought consistent with mesothelioma. When his symptoms worsened, a second chest x-ray documented a left pleural effusion, subsequently treated with chest tube placement and drainage. After recovering from the acute episode, a second CT scan in July demonstrated a collapsed left lung, a persistent left pleural effusion and numerous large tumors. The official report states: â��the largest pleura bases (sic) mass in the left upper lobe laterally measures 2.976 cmâ�¦The largest mass in the left lower lobe posteriorly measures 5.39 cmâ�¦There are at least 18 pleural based masses present on the left.â��
FV then underwent bronchoscopy, left video assisted thoracotomy with pleural biopsies, and pleurodesis. The initial pathology report of the biopsy specimen suggested most likely mesothelioma, but a review at The Armed Forces Institute of Pathology confirmed not mesothelioma, but, as the note describes:
Pleura, left, biopsy: Metastatic papillary adenocarcinoma, of pulmonary origin.
His local doctors also sent the pathology slides to Brigham and Womanâ��s Hospital in Boston, a research center for mesothelioma, where, in July the tumor was thought most likely a papillary adenocarcinoma of the lung, staged at IIIB.
In late July 2003 FV decided to consult with Dr. David Sugarbaker, a thoracic surgeon and expert in pleural lesions at Brigham and Womenâ��s. At Brigham, CT scans of the abdomen and pelvis were clear. A total body PET scan confirmed the extensive left pleural lesions but showed no evidence of distant metastatic disease. Since the disease seemed localized to the chest, Dr. Sugarbaker proposed the tumor be treated as if it were a pleural lesion like a mesothelioma with extensive surgery, including removal of the entire left lung, the pericardium and the left side of the diaphragm.
This debilitating approach seemed excessive, so FV, upon returning home, consulted with an oncologist in the Washington DC area who believed the situation should be approached initially not with surgery but instead with an aggressive chemotherapy regimen. If the tumors regressed significantly, a less aggressive procedure might be feasible. The oncologist also consulted with three additional thoracic surgeons, including one within the NIH system, who felt the surgical approach suggested in Boston overly aggressive, and that the tumor should be treated as a primary lung cancer, not as a pleural tumor like mesothelioma. All believed chemotherapy should be the initial therapy of choice.
FV then traveled to New York for a consultation with the Chief of Thoracic Surgery at Memorial Sloan-Kettering, who concurred that the disease appeared to be lung cancer that had spread to the pleura, not the other way around. She recommended chemotherapy as the first line treatment, perhaps followed by surgery.
With the debate resolved, in September 2002 FV began a four-cycle course of Gemzar and carboplatin. After he completed his last treatment in November 2002, a CT scan revealed some slight worsening in the largest tumor, despite the chemotherapy:
The cystic structure in the posterior left upper lungâ�¦measuring 4.8 x 6 cm, compared to prior measurements of 4.5 and 5.9 cm. The pleural based lateral left upper lung lesions are also essentially unchanged, measuring 2.6 and 2.9 cm, compared to prior measurements of 2.8 and 2.9. The rest of the pleural-based masses and left basilar pulmonary nodules are unchangedâ�¦
Since the disease had progressed, even if slightly, FV began investigating alternative approaches, learned of our work and consulted with me in mid December 2003. At the time, he generally felt well and seemed to have recovered from chemotherapy quickly. Thereafter, he began his nutritional regimen with great dedication and superb compliance. When I saw him for a return office visit three months later, in April 2004, he reported feeling â��great.â�� Two months later, in June 2004, PET/CT scan testing confirmed improvement in his disease, as he followed only his nutritional regimen. The CT describes:
CT-CHEST: Numerous pleural-based masses, and small ones adjacent to the pericardial surface are presentâ�¦Most of these lesions appear marginally smaller than they previously did (note: compared to the November 2003 CT scan), by a few millimeters. The largest lesion, located posteromedially in the mid-chest, again appears largely necroticâ�¦
Soft tissue abnormality in the left upper quadrant of the abdomen, anterior to the splenic flexure, appear slightly smaller in overall bulk as compared to the prior studyâ�¦
Note that the prior radiology reports had not described the lesion in the abdomen, a metastatic focus which would confirm stage IV, not stage III disease. Apparently the lesion had been evident on prior scans, but not described in the official report.
The overall summary of the June PET/CT states:
IMPRESSION: PET scans shows numerous pleural-based pathologic foci in the left hemithorax, consistent with numerous foci of metastatic neoplasm. A lesion at the anterior aspect of the left upper quadrant of the abdomen, or immediately adjacent diaphragmatic surface is presentâ�¦.
CT examination of the chest shows minimal decrease in the overall size of the numerous pleural-based masses in the left hemithorax, and in the region located either in the left upper quadrant of the abdomenâ�¦
So, while the PET confirmed residual active cancer, the CT scan indicated universal, though slight, reduction in the many tumors with advancing necrosis in the largest remaining tumor.
Since that time, FV has continued his nutrition regimen vigorously, and has done extremely well. He has declined all invitations for follow up CT and PET/CT scanning, stating he wouldnâ��t change his treatment regardless of what the tests show. So, while we donâ��t have clear evidence of additional tumor regression, his continued survival, now at three years since he began his nutritional regimen, and his excellent general health speak for themselves.
His course has had only one complication. In the spring of 2006, FV felt well enough to take a trip to Europe with his wife. Upon arriving abroad, he developed severe headaches requiring hospitalization. After CT scans and MRIâ��s of the head showed nothing, he was eventually diagnosed with a cerebrospinal fluid leak. He returned to the United States, the problem eventually resolved and once again, FV is back to his usual state of well being.
In analyzing this case, itâ��s important to keep in mind that although the disease was originally classified as stage IIIB lung cancer, the PET/CT scans in June 2004 clearly showed an abdominal lesion that would indicate stage IV metastatic disease. Though evident on prior scans, this lesion was not mentioned in the formal reports. Also, a CT scan done weeks after FV completed his four cycles of aggressive chemotherapy showed no reduction in any of the tumors, and some enlargement. Only after he had followed nutritional program some six months did the PET/CT scans document regression in all tumors, and the appearance of significant necrosis in the largest.
For patients with stage IV non-small cell lung cancer, studies show chemotherapy improves average survival by about one month over supportive care only. Even with the newest most aggressive chemotherapy regimens, median survival is still only 9-10 months, with, depending on the regimen, a mere 25-40% of patients living 1 year. (3) Virtually none survive 5 years. FVâ��s 3-year survival and excellent health are even at this point extraordinary.
Patient RZ: Lost to Follow-up After Tumor Regression
Patient RZ was one of the first patients I treated with a diagnosis of metastatic lung cancer after I opened my practice in late 1987. He had smoked cigarettes heavily for 28 years, before quitting some 15 years prior to developing cancer. Otherwise his health had generally been good when in early 1987, he first developed persistent chest pain and cough. When his symptoms did not resolve, he consulted his local physician. After an x-ray revealed a right lung mass, in March 1987 he underwent bronchoscopy with biopsy confirming adenocarcinoma of the lung. A CT showed two tumors, one in the right apex, the second in the right hilum, though the left lung appeared clear. Since the disease appeared limited to the right lung, surgery was immediately suggested. RZ initially refused all conventional intervention but when his symptoms worsened he agreed to proceed with surgery. In July 1987 he underwent a right pneumonectomy, with the pathology report describing a 2.5 cm lesion, consistent with poorly differentiated adenocarcinoma, extensively invading the hilar lymph nodes. He was staged at III, and proceeded postoperatively with a course of radiation to the chest totaling 4500 rads.
RZ subsequently did well until September 1988, when he developed persistent headaches and olfactory hallucinations described as putrid foul smells. A CT scan of the head in October 1988 revealed multiple tumors located in the temporal, right frontal and left occipital areas with associated edema.
His doctor prescribed the steroid Decadron to reduce the cerebral swelling but the symptoms did not improve. In early November 1988 he proceeded with a ten-day course of radiation to the head, ultimately receiving a total of 3000 rads, with some improvement in his symptoms. In December 1988, a month after completing radiation, a CT scan of the head revealed the situation had worsened despite treatment:
Multiple, bilateral intracerebral ring-enhancing lesions, consistent with metastases. In addition there appears to be an early left cerebellar hemisphere lesion. Many of these were noted on Oct---1988. However, several new small areas of abnormality are identified on the present exam, not previously seenâ�¦
At this point, with his disease progressing, RZ, who already had been investigating alternative approaches to cancer, came to New York for a consultation with me. He reported severe neurological symptoms, including headaches, that had recently recurred despite Decadron. He thereafter began his nutritional program with initial great enthusiasm, and in January 1989, after he had completed but a month on his nutritional program, a CT scan showed significant improvement:
When compared to the last previous exam of 12â��88, there has been diminution both in the size and number of the visualized intracranial lesions. No new areas of abnormality are seen.
According to his oncologistâ��s notes, a bone scan in March 1989 showed clearing of previous noted bone lesions, though I do not have the actual radiology report.
At that point, RZ was symptom-free and strong enough to return to his stressful job. Unfortunately, he felt so well he became careless with his supplement regimen and diet, and by April 1989 was by his own admission less than 50% compliant with his overall protocol. Not surprisingly, after his neurological symptoms returned with a vengeance, a CT scan in May 1989 revealed worsening disease:
Increased intracranial edema and size of previously reported intracranial metastases when compared to 3---89.
After a discussion with me about the need for perfect compliance, RZ resumed his full program as prescribed. His symptoms rapidly improved and a CT scan in July 1989 demonstrated reduction in all his brain tumors:
The three metastatic lesions on the 5---89 CT have decreased in size. No new metastatic lesions are seenâ�¦.
With the return of his good health, RZ again became careless with his program. I last saw him in September 1989, nine months since our first session, when after several weeks of poor compliance his neurological symptoms had returned. Thereafter, he was lost to follow-up. He had no family that I knew of, and despite my efforts, I could never learn what happened to him
In this case, the patientâ��s disease, before he had consulted with me, had progressed despite intensive radiation to the brain. After he began his nutritional program the brain (and apparently the bone) lesions regressed, only to worsen when compliance fell off. When RZ became more adherent to the prescribed regimen, the brain tumors again improved. Ultimately, he lacked the dedication and discipline to stick to the program as required.
DeVita reports a median survival of 15-18 weeks for patients with multiple metastatic brain lesions from non-small cell lung cancer treated with intensive radiation. (4) So, despite his compliance problems, this patientâ��s 36+ weeks of survival beat the odds.
And, again despite his lapses, I thought this patient of interest since he remains one of the few I have ever treated with brain metastases from a primary lung neoplasm. Though in recent years occasional patients in this situation have contacted our office seeking information about our therapy, most are so far into the terminal stages of their illness we canâ��t justify trying to treat them. For better or worse, in this age of aggressive oncology, patients facing this diagnosis invariably get shunted frantically and immediately into multi agent chemotherapy and radiation. Only after months of futile treatment, when the disease explodes and the patient weakens, do they begin looking into alternative options. By then, it is too late. I believe we could help many diagnosed with this terrible condition if, like RZ, they came earlier in their course, but over the last decade this has simply not been the case. And we do not accept patients for treatment whom we believe we canâ��t help.
Patient SV: A 5.5-Year Survivor
Patient SV is a 44-year old woman who had been in good health when in 1998, she first noticed the need to repeatedly clear her throat, a symptom she attributed to persistent postnasal drip. By 1999, she had developed a mild non-productive cough associated with a gradual decline in energy, attributed to the demands of tending to her new baby.
During 1998 and 1999, SV repeatedly consulted her primary care physician because of ongoing respiratory symptoms, but she was reassured she had nothing more serious than a recurrent viral syndrome that warranted no further testing. When the cough and fatigue persisted, she was ultimately referred to an allergist who thought the symptoms were unrelated to allergies. However, no chest x-ray was suggested.
The cough and associated problems continued into 2000. At one point in 2000 during a family visit, after hearing the cough, the patientâ��s sister, a medical professional, insisted a chest x-ray and TB testing be done. Subsequently, when a TB skin test was negative, SV chose not to follow up with the chest x-ray.
A month later, in October 2000, SV developed a significantly worsening cough associated with a high fever and severe fatigue. She visited her doctor who after an exam announced she once again had a viral infection. When, at end of November 2000, the cough worsened, she requested an x-ray, which her doctor told her showed pneumonia. When the symptoms did not improve after a second course of antibiotics, a repeat chest x-ray revealed a persistent left lung infiltrate. A CT at that point then showed a large lesion in the left lower lung consistent with primary lung cancer.
SV was referred to a pulmonologist for bronchoscopy and biopsy, which confirmed adenocarcinoma of the lung. With the diagnosis finally made, the patient met with a local oncologist who ordered a full metastatic work-up. A CT scan of the abdomen and pelvis showed a porta hepatis mass that was considered insignificant. In January 2001 SV decided to consult with an oncologist and lung cancer specialist at the Mary Hitchcock Medical Center in New Hampshire. At Hitchcock, after a PET scan revealed only the large lung tumor, with no evidence of metastatic disease, the physician recommended surgery for resection of the lesion as soon as possible.
In January 2001 SV then met with the Chief of Thoracic Surgery at Memorial Sloan-Kettering in New York. Repeat bronchoscopy at Memorial with transbronchial biopsy confirmed moderately differentiated mucin secreting adenocarcinoma. Repeat PET scan showed a 5.5 cm lesion in the left lung as well as a 1 cm secondary satellite lesion, but CT scans of the head, abdomen and pelvis were clear. Subsequently, in February 2001 at Memorial, SV underwent left lower lobectomy with the pathology report describing a tumor 6.2 cm in diameter, consistent with moderately differentiated mucinous adenocarcinoma. Tumor had invaded three of eight lymph nodes evaluated, a very dire prognostic indicator.
According to the patient, the Memorial surgeon warned that neither chemotherapy nor radiation would be very helpful long term and should be held in reserve until the disease recurred, as it most likely soon would. SV decided she nonetheless wished to meet with an oncologist, so she consulted at Memorial with a physician pursuing a vaccine research study designed for patients with stage III lung cancer. At the same time, she began investigating our work, which a friend had discussed with her. The same day she first consulted with me in March 2001 she also visited Memorial Sloan-Kettering to discuss both chemotherapy and the vaccine trial. The physicianâ��s note from that day clearly expresses the poor prognosis SV faced:
I had a lengthy discussion with the patient and her husband regarding the situation. The patient already understands that because of her stage, she is at risk for recurrence in the future. We discussed in detail the role of adjuvant chemotherapy and radiation therapy. In one meta-analysis published in 1995, cisplatin based chemotherapy improved the rate of survival by 5% after five years. Radiation typically has been described as improving local control without improvement in survival due to the risk of systemic metastases. One recent trial published in the New England Journal indicated that the addition of chemotherapy with etoposide and cisplatin to adjuvant radiation did not improve survival.
In the same note, though the oncologist clearly admits that radiation and intensive chemotherapy essentially do little, two sentences later he nonetheless recommends the patient be aggressively treated anyway!
For this patient, who is quite young, I would probably favor aggressive treatment, providing her with some adjuvant chemotherapy with a cisplatin-based regimenâ�¦In addition, I also discussed with her clinical trials...
The vaccine trial, offered as an option to aggressive chemotherapy, turned out to be a preliminary pilot study. Then, after her consultation with me and the Sloan-Kettering physician, SV met with her local oncologist, who told her that even with aggressive chemotherapy and radiation, only one in five patients with her specific diagnosis and stage lived beyond a â��couple years.â��
Since little data favored any of the orthodox treatments, SV decided to forgo all conventional approaches and begin our nutritional regimen. When we met for our second session some days later, she handed me a copy of the consent form for the Memorial Sloan-Kettering clinical study. I found it informative in that the researchers clearly discuss the aggressive nature of lung cancer, and its notorious resistance to standard approaches:
Non-small cell lung cancer is a difficult disease to treat. Even after curative surgery, there is a high likelihood of the cancer returning. Chemotherapy and radiation are sometimes given after surgery to decrease the chance that the cancer will come back; however it is unclear whether this really helps. In this study, we are trying to develop a different approach to treat patents with non-small cell lung cancer after surgery. We are testing a new vaccine designed to boost your immune system against your cancerâ�¦
SV then began my therapy with great determination and great dedication. A follow up CT scan from February 2003 did reveal a 2-3 mm nodule in the periphery of the right lung. A follow up scan in September 2003 showed that â��The nodule in the periphery of the right lung posteriorlyâ�¦.remains unchanged and stable.â�� Repeat CT scans in August 2004 reported â��A stable 2-3 mm pulmonary nodule is seen in the right lower lobe. No new nodules are seenâ�¦â�� Her most recent scans in October 2005 were completely clear.
Today, more than 5.5 years first beginning her nutritional therapy, SV remains compliant and in good health with no evidence of recurrent disease. She continues to follow up periodically with her local oncologist, who seems very supportive of the road she has taken.
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1. Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo, DL, Jameson JL. Harrisonâ��s Principles of Internal Medicine, 16th Edition. New York: McGraw-Hill; 2005:506.
2. DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles and practice of oncology, 6th Edition. Philadelphia: Lippincott Williams & Wilkins; 2001:928.
3. DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles and practice of oncology, 6th Edition. Philadelphia: Lippincott Williams & Wilkins; 2001:969.
4. DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles and practice of oncology, 6th Edition. Philadelphia: Lippincott Williams & Wilkins; 2001:973.